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Phytoncides (Wood Essential Oils) Induce Human Natural Killer Cell Activity
Abstract
To explore the effect of forest bathing on the human immune system, we investigated the effect of phytoncides (wood essential oils) on natural killer (NK) activity and the expression of perforin, granzyme A and granulysin in human NK cells. We used NK-92MI cell, an interleukin-2 independent human NK cell line derived from the NK-92 cell, in the present study. NK-92MI cells express the CD56 surface marker, perforin, granzyme A, and granulysin by flow cytometry and are highly cytotoxic to K562 cells in chromium release assay. Phytoncides significantly increase cytolytic activity of NK-92MI cells in a dose-dependent manner and significantly increase the expression of perforin, granzyme A, and granulysin in the NK-92MI cells. Phytoncides also partially, but significantly, restore the decreased human NK activity and the decreased perforin, granzyme A, and granulysin expression in NK-92MI cells induced by dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide. Pretreatment with phytoncides partially prevents DDVP-induced inhibition of NK activity. Taken together, these data indicate that phytoncides significantly enhance human NK activity and this effect is at least partially mediated by induction of intracellular perforin, granzyme A, and granulysin.
... However, as the demand for these healing programs continues to grow, researchers face the challenge of designing indoor forest healing experiences, including virtual reality simulations, to cater to individuals who are unable to access actual forests. Pivotal to this endeavor is the understanding of phytoncides, which are natural volatile organic compounds (NVOCs) emitted by trees and plants that have been identified as key contributors to the beneficial effects of forest environments on human health [7][8][9]. ...
... These organic volatiles constitute essential components of the chemical communication system utilized by the plant kingdom, playing pivotal roles in both plant defense mechanisms and interspecies communication [10,11]. Beyond their ecological significance, phytoncides have garnered attention for their potential therapeutic properties in humans, with growing research indicating their positive effects on mental and physical health, such as the enhancement of immune function, antiinflammatory effects, and alleviation of depression [7][8][9]. In the face of global urbanization Science (NIFoS) in Seoul, Republic of Korea. ...
This study addresses the growing need for phytoncide studies, driven by the demand to design indoor forest healing programs, including virtual reality experiences, for patients unable to visit actual forests. Previous studies have struggled to establish consistent phytoncide emission patterns in outdoor forest environments owing to varying microclimates and abiotic factors. In addition, the traditional gas chromatography–mass spectroscopy (GC-MS) method presents field measurement challenges, whereas the selected ion flow tube (SIFT)-MS method offers improved efficiency. This study concentrated on a controlled phytotron environment and compared the GC-MS and SIFT-MS findings, revealing similar emission trends with slightly higher SIFT-MS concentrations. Daily phytoncide emissions fluctuated with light intensity and abiotic stressors. Both methods consistently detected pinenes, primarily emitted by Pinus strobus L. seedlings, in the phytotron. Statistical analysis confirmed the compatibility between GC-MS and SIFT-MS results, supporting the use of SIFT-MS for forest phytoncide assessment. In the second phase, the phytoncide emissions were assessed indoors, outdoors, and in the phytotron, highlighting the superiority of the phytotron under controlled conditions. Despite certain limitations, this study underscores the value of phytotron-based measurements for indoor forest healing programs and the potential adoption of SIFT-MS in future field-based phytoncide research.
... NK cells and their subsets were altered by stress hormones, as verified in this study, suggesting that the reduction of epinephrine and cortisol activates NK cells (Bodner et al., 1998;Tønnesen et al., 1987). Li et al. (2006) stated that the target cells are killed when phytoncides are used to treat an NK cell line. They also suggested that phytoncides increase NK cell activity by inhibiting cortisol. ...
... They also suggested that phytoncides increase NK cell activity by inhibiting cortisol. Moreover, NK cells activated by increased phytoncide levels are related to increased perforin, granzyme B, and granulin (Li et al., 2006). Thus, NK cells were influenced by their subsets. ...
This study aimed to identify neuroendocrine substances and natural killer (NK) cells, including their subsets and receptors, to determine whether phytoncides scented in an urban hospital could help improve stress in cancer survivors. Fifty-five gynecological cancer survivors were assigned to either the control group (CG, n= 28) or phytoncide group (PTG, n= 27). The PTG meditated by lying down in a space scented with phytoncide for 1 hr a day, 5 days a week for 8 weeks. Stress levels in both groups were high prior to the experiment and decreased by 9.31%± 45.98% ( P = 0.003) only in the PTG after the experiment. Although the parasympathetic nerve activity of the PTG increased, the epinephrine and cortisol levels were significantly ( P < 0.001) decreased by 5.29%± 25.5% and by 24.94%± 11.62%. Moreover, the PTG showed a significant increase in the levels of NK cell subsets after 8 weeks, whereas there was no improvement in the CG. In conclusion, phytoncide fragrance reduces stress, increases the number of NK cells and their family even in a nonforest environment, and improves innate immunocytes in gynecological cancer survivors; parasympathetic nerve activity and cortisol hormones play critical roles in this process. That is, a phytoncide essential oil helps to stimulate changes in immunocytes’ mobility by affecting the human nervous and endocrine systems, thereby providing relief for psychological stress among cancer survivors who previously had cancer cells.
... Through tangible interaction, we can recreate the experience of communicating with people and nature and embed elements of this at home. Studies have shown how multisensory interaction (including smell-changing) can change human behaviour [23,33], have anti-depressive effects [63], and enhance their overall wellbeing [32]. Our motivation also stems from the call of researchers and practitioners in the HCI and interaction design community (shared by Dalsgaard [8]) indicating that developing new forms of remote social communication is one of the ways to address "How can we contribute to shaping the new normal?" ...
... Such interactive modalities did not only help them in improving their mental wellbeing, but also align with relevant studies showing the health impacts of reduced exposure to nature, interaction with others, and loss of indicators of time [2,4] where people miss touching, seeing, hearing, and smelling the world. These design concepts also tie well with previous work on how such challenges could be tackled through multisensory interaction (including audio feedback [43], colour-change [10], and smell-change [23,33]) and enhance the overall wellbeing [32]. Therefore, if we aim to design for users' wellness, we should be designing more of such senses-engaging modalities, and less of buttons, screens, and motorized machine interactions. ...
This paper describes our collaborative journey of creating everyday interactive artefacts to help us think, reflect, and live through self-isolation. Through a co-design approach, we designed interactive homeware objects (that we collectively refer to as ‘COVIDware’) to address the challenges of isolation during the pandemic. Five artefacts were developed by self-isolated designers as interactive art installations. We discuss how each creator reflected on her design concept, process, and encounter through concepts of critical making, speculation, and engagement via in-the-isolated-wild deployments. By empowering early researchers/enthusiasts to design ‘with’ smart-materials, and off-the-shelf items, we reflect on how these homey interfaces can enhance people’s wellbeing beyond screen-based interactions. Despite not collaborating in the making process, our findings from the designer’s making process show how all the designed artefacts shared attributes of biophilic design, imperfection, and unconventional interactions with the overarching goal of promoting wellbeing, and meaningful connection with nature, self, and others.
... It is the total effect from all five senses: senses of sight, smell, hearing, touch and taste. In fact, sense of smell by breathing in volatile organic substances, called phytoncides from trees, such as ¡-pinene and limonene has a bigger effect [27,59]. My research team found that phytoncides released from trees significantly increased human NK activity and the intracellular levels of perforin, GrA, and GRN in human NK cells both in vitro [59] and in vivo [27]. ...
... In fact, sense of smell by breathing in volatile organic substances, called phytoncides from trees, such as ¡-pinene and limonene has a bigger effect [27,59]. My research team found that phytoncides released from trees significantly increased human NK activity and the intracellular levels of perforin, GrA, and GRN in human NK cells both in vitro [59] and in vivo [27]. Phytoncide exposure significantly decreased the concentrations of adrenaline and noradrenaline in urine, indicate that phytoncide exposure and decreased stress hormone levels may partially contribute to increased NK activity [27]. ...
Humans have enjoyed forest environments for ages because of the quiet atmosphere, beautiful scenery, mild climate, pleasant aromas, and fresh, clean air. In Japan, since 2004, serial studies have been conducted to investigate the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. My research team has established a new medical science called Forest Medicine. The Forest Medicine is a new interdisciplinary science, belonging to the categories of alternative medicine, environmental medicine and preventive medicine, which studies the effects of forest environments (Forest bathing/Shinrin-yoku) on human health. It has been reported that Forest bathing/Shinrin-yoku has the following beneficial effects on human health:
1 Shinrin-yoku increases human natural killer (NK) activity, the number of NK cells, and the intracellular levels of anti-cancer proteins, suggesting a preventive effect on cancers.
2 Shinrin-yoku reduces blood pressure and heart rate showing preventive effect on hypertension and heart diseases.
3 Shinrin-yoku reduces stress hormones, such as urinary adrenaline and noradrenaline and salivary/serum cortisol contributing to stress management.
4 Shinrin-yoku increases the activity of parasympathetic nerves and reduces the activity of sympathetic nerves to stabilize the balance of autonomic nervous system.
5 Shinrin-yoku improve sleep.
6 Shinrin-yoku increases the levels of serum adiponectin and dehydroepiandrosterone sulfate.
7 In the Profile of Mood States (POMS) test, Shinrin-yoku reduces the scores for anxiety, depression, anger, fatigue, and confusion, and increases the score for vigor, showing preventive effects on depression.
8 Shinrin-yoku may apply to rehabilitation medicine
9 Shinrin-yoku in city parks also has benefits on human health.
10 Shinrin-yoku may have preventive effect on COVID-19 by boosting immune function and by reducing mental stress.
Taken together, these findings suggest that Shinrin-yoku may have potential preventive effects on non-communicable diseases.
... Previous studies reported that forest bathing enhanced NK cell activity, the number of NK and NKT cells, and intracellular anti-cancer proteins in lymphocytes [35][36][37]. Li et al. [35] reported that the increased NK activity was the leading cause of aromatic volatile substances derived from trees, called phytoncides, such as α-pinene and limonene. If phytoncide is inhaled while bathing in the forest, it is well known that it reduces cortisol, a stress hormone. ...
... Previous studies reported that forest bathing enhanced NK cell activity, the number of NK and NKT cells, and intracellular anti-cancer proteins in lymphocytes [35][36][37]. Li et al. [35] reported that the increased NK activity was the leading cause of aromatic volatile substances derived from trees, called phytoncides, such as α-pinene and limonene. If phytoncide is inhaled while bathing in the forest, it is well known that it reduces cortisol, a stress hormone. ...
Background: Forest bathing and aerobic exercise are known to be factors that increase natural killer (NK) cell, but it is considered to provide a greater effect when the two factors are combined. To date, it has not been studied whether aerobic exercise combined with forest bathing can further increase innate immunocytes, including NK cell. Therefore, this study investigated the effect of aerobic exercise + forest bathing on NK cell and whether stress hormones (epinephrine and cortisol) are involved in this physiological process. In addition, this study tried to confirm whether the mixed effect of the two had a more positive effect on cardiorespiratory endurance as well as body composition in the elderly men. Methods: Thirty-two participants were randomly assigned to one of four groups: control group (CON, n = 8) which was not provided with any intervention, exercise group (EXE, n = 8) which performed treadmill exercises without phytoncide, phytoncide group (PHYT, n = 8) which was provided with phytoncide intervention, and exercise + phytoncide group (EXE + PHYT, n = 8) which performed treadmill exercises and was provided with phytoncide. Treadmill exercises and phytoncide exposures were performed for 45~60 min a day, 3 days a week for 12 weeks. Results: Compared with CON, (1) the leucocytes and lympocytes of EXE, PHYT, and EXE + PHYT showed positive changes. Specifically, total NK cells, NKT cells, and NKG2D + NK of the EXE + PHYT increased after 12 weeks of intervention. (2) The cortisol concentrations of EXE, PHYT, and EXE + PHYT showed decreasing changes, whereas the epinephrine concentration were significantly increased. (3) Although there were no changes in the muscle mass of EXE, PHYT, and EXE + PHYT, cardiorespiratory endurance was significantly increased in those groups. In addition, the body weight, fat mass, and fat percentage significantly decreased only in the EXE + PHYT. Conclusions: This study confirmed that forest bathing and aerobic exercise positively affected immunocyte function in elderly men. It also found that the improved results from forest bathing + treadmill walking were caused by an increase in cardiorespiratory endurance by increased epinephrine concentrations. In addition, this increased cardiorespiratory endurance can be interpreted as significantly reducing the body weight and fat in the group that participated in the exercise combined with phytoncide exposure.
... Elderly patients with chronic pulmonary diseases gained more health benefit from breathing exercises when performed in forests (Bing et a., 2016). This can be attributed to breathing in phytoncides, which are antimicrobial volatile organic compounds derived from trees, which improves immunity (Ohtsuka et al., 1998;Li et al., 2006). It has also been reported that psychiatric treatment for children was more effective when paired with nature therapy at a beach (Berger and Tiry, 2012). ...
... In ancient Rome, it was common for people to periodically take refuge in forested areas to deal with urban congestion (Glacken, 1967). Some researchers believe the healing powers of nature is primarily due to phytoncides, a volatile substance emitted by plants Li et al. (2006). Song et al. (2016) discovered that indoor exposure to forest derived phytoncides could increase NK cell activity and improve overall immunity function. ...
The Coronavirus disease-2019 (COVID-19) pandemic has affected over 200 countries, forcing governments to impose lockdowns to contain the spread of the disease. Although effective in reducing infection rates, the lockdowns have also resulted in a severe negative impact on mental health throughout the world; Setting the foundation for mental illnesses to become the next “silent” pandemic. This study attempts to determine a self-care method of ensuring mental health during the COVID-19 pandemic, especially for those living under lockdown. We evaluated the potential of physical exercise (in a nature setting) and nature therapy in improving mental wellbeing, among young adults with either stress, anxiety or depression symptoms. The study involved thirty subjects, who were equally divided into a nature-exercise group and a nature therapy group. The participants were briefed on the activities that they were to perform on a daily basis, and both groups performed their assigned activities concurrently for one week (27th April 2020 to 3rd May 2020) at urban greeneries accessible to them (rooftop parks, neighbourhood parks, home gardens). We used the depression, anxiety and stress scale – 21 items (DASS-21) to evaluate the mental health status of participants, once before beginning the study (baseline readings) and once at the end of the study (after a week of nature-exercise/nature therapy). There was a statistically significant reduction in stress, anxiety and depression symptoms for both the nature-exercise and nature therapy groups. However, when evaluating the effectiveness of exercise and nature therapy in treating stress, anxiety and depression symptoms on a case-by-case basis, it was discovered that nature therapy was more effective in treating mental health issues. Hence, nature therapy has the potential to be a form of preventive medicine, namely in preserving mental health during the COVID-19 crisis.
... Most of the current literature surrounding therapeutic uses of phytoncides makes use of forest bathing as an intervention, and numerous studies have demonstrated its effectiveness in improving immune functioning via increases in NK cells, perforin, and granulysin [9,12,13]. Despite these advancements, the mechanisms by which specific phytoncides influence immune functioning remain relatively understudied [14]. ...
Background: Forest bathing is a traditional Japanese custom that involves immersing oneself in forest settings for extended periods. It is recognized for its positive impacts on psychological and physiological well-being. Phytoncides play a key role in the benefits of forest bathing and have begun to be investigated for their immunotherapeutic potential. It is important to investigate their immunomodulating effects within both forest and clinical settings.
Purpose: We conducted a systematic review and meta-analysis to investigate the effects of phytoncides on immune functioning.
Materials and methods: A PICO-SD framework was used to screen studies from databases, including PubMed, Web of Science, Scopus, Cochrane, and Trent University’s Omni portal. Selection criteria involved studies of adults aged 18+ exposed to phytoncides, comparing those exposed with control groups. The outcomes of eligible studies focused on immunological measures, excluding survey and qualitative research. Risk of bias was assessed using the ROBINS-I tool for non-randomized controlled trials and the ROB-2 for randomized controlled trials. Six studies (79 participants) were included in this meta-analysis. The meta-analysis included standardized mean difference effect sizes (Cohen’s d) with a random effects model using the Hartung-Knapp adjustment and 95 % confidence intervals for continuous data.
Results: This review found favourable immunological outcomes of phytoncide treatment, including increases in NK cells, T-cells, and cytotoxic effector molecules. Meta-analysis indicated a significant increase in NK cell activation (Effect Size: 2.50; 95 % CI [1.94–3.05]; p < 0.05; I2 = 50.47 %).
Conclusions: The evolving landscape of phytoncide research calls for randomized controlled trials using specific phytoncides to establish the efficacy and safety of phytoncides in diverse healthcare settings.
... 5 These oils comprise different molecules, such as monoterpenes, sesquiterpenes, and phenols, 6 which possess antimicrobial effects, enhance the immune system, and provide stress relief. [7][8][9] In particular, essential oils such as lemongrass oil and May Chang oil are effective against Candida albicans, a type of vaginitis-causing fungus. [10][11][12] Certain essential oils possess a deodorizing effect on various substances, including ammonia gas. ...
In this study, antimicrobial and deodorizing nanofibrous composite membranes based on natural substances were developed for use in feminine sanitary napkins. Plant-derived natural essential oils, such as lemongrass oil and May Chang oil, were incorporated into polyvinyl alcohol nanofibers using emulsion electrospinning. The fiber morphology, oil distribution, and pore size distribution of the nanofibrous composite membranes were examined. The antimicrobial and deodorizing effects, tensile properties, and release behavior of the functional ingredients from the composite membranes were investigated to examine their use in sanitary napkins. Core–sheath nanofibers, in which lemongrass oil or May Chang oil was uniformly distributed within the fiber core, were fabricated using various oil contents. The essential oil-loaded nanofibrous composite membranes contained pores ranging from 0.130 to 1.349 µm in size. The release profiles of the essential oils from the composite membranes over an 8 h period demonstrated a continuous release of citral and limonene. Composite membranes containing either lemongrass oil or May Chang oil exhibited outstanding antimicrobial effects against vaginal pathogens, such as Candida albicans and Staphylococcus aureus, despite their low oil content. Deodorizing effects against ammonia gas were observed at oil contents higher than that required to achieve antimicrobial effects. The composite membranes exhibited lower Young’s modulus and greater elongation at break values under wet conditions compared to dry conditions. Our findings demonstrate that antimicrobial and deodorizing nanofibrous composite membranes based on plant-derived essential oils have the potential for use in feminine hygiene products.
... 12 When inhaling the smells of the forest, people take in volatile essential tree oils called phytoncides that have antimicrobial qualities and have also been shown to boost immunity by increasing the numbers of natural killer cells; this boost lasted for more than a month after the forest trip. 13 Viewing forest landscapes has been shown on functional MRI to be associated with changes in right prefrontal cortical activity that is linked to physiological relaxation. 14 Beyond the physical health benefits of nature immersion, research has also shown that time in nature enhances mental health. ...
Background
Physician burnout has reached epidemic proportions. Although burnout is rooted in systems, practices for physician wellbeing and community can address exhaustion, burnout, and isolation. Inspired by the Japanese practice shinrin-yoku, forest therapy/bathing (FT) is a nature immersion practice that improves wellbeing in a group setting.
Objective
This program offered guided FT experiences to frontline faculty physicians in the Department of Medicine and evaluated potential for impact on burnout, resilience, and community.
Methods
Faculty physicians were recruited via email invitations to a free Forest Therapy group experience in the Arnold Arboretum in Boston, MA. Participants completed pre-and post-course surveys and evaluated its value as a community experience. Surveys measured burnout, resilience, and qualitative feedback on the experience.
Results
Twenty-seven faculty completed the baseline survey, twenty-three faculty participated, with 19 survey respondents. At baseline, 85% reported feeling burned out at least once a month. 46% reported feeling burned out more than a few times a month. 83% of participants responded that forest therapy could help them with the feeling of being burned out from work. Post-intervention, 100% of participants rated the experience as very or extremely valuable. 96% of participants reported they were interested in more frequent forest therapy sessions. 100% of participants would recommend this practice to other faculty. 70% of respondents reported the program could help them with burnout. Despite high baseline resilience, 94% of participants reported that forest therapy could help with stressful events and setbacks. Post-intervention, participants reported feeling relaxed, at peace, and calm.
Conclusion
This pilot demonstrates feasibility and acceptability for physicians of FT. Participants would consider recommending FT to their colleagues, and agreed that FT can help with wellbeing, and expressed enthusiasm for the community experience. This program may also be successfully incorporated into programs for leadership, teambuilding, and support after adverse events.
... Increased exposure to green space might help mitigate the risk of hypertension by controlling the aging process of blood vessels, the expansion and hardening of the aorta and carotid arteries, and the thickening of the intima (Lane et al., 2017). Additionally, some studies suggested that plants could release some antibacterial volatile organic compounds, which might reduce blood pressure (Dayawansa et al., 2003;Li et al., 2006). In our subgroup analysis, we observed that green space appeared to have a stronger regulatory effect on health in males, participants younger than 60 years old and participants with physical activity <150 min/w. ...
... NVOCs are well-known phytoncides that are mixtures of several terpenes. Unlike many VOCs that cause air pollution, phytoncides improve human health [6][7][8][9]. The representative health-promoting effects of phytoncides include antibacterial and anti-inflammatory effects, stress reduction, depression relief, and aggressive tendency reduction [10]. ...
Conventional gas chromatography-mass spectrometry (GC-MS) analysis methods for measuring the concentration of phytoncides in forests are limited because of the need for an extended human presence in forests, the risk of errors, and contamination. To overcome these issues, this study introduces real-time measurement devices and selected ion flow tube mass spectrometry (SIFT-MS) as potential replacements. This study was conducted in the Hongneung Experimental Forest between 19 and 21 November 2019. A correlation analysis and independent samples t-test were performed to compare the GC-MS and SIFT-MS techniques. The diurnal patterns and trends in the phytoncide concentrations analyzed using the GC-MS and SIFT-MS methods were similar, suggesting the potential replacement of GC-MS with SIFT-MS. While both methods revealed similar major components in the daytime nonvolatile organic compounds (NVOCs), with pinenes comprising approximately half of the total percentage, the 24 h SIFT-MS analysis indicated reduced proportions of pinenes and benzaldehyde, along with the detection of more diverse NVOC compounds at night. Additionally, the studies indicated that GC-MS exhibited slightly higher selectivity, resulting in the detection of fewer NVOC compounds with SIFT-MS. The correlation analysis between the microclimate indicators and phytoncide measurement methods revealed differences: GC-MS with a mini pump showed positive correlations with fine dust and industrially derived VOCs, while the 24 h real-time measurements exhibited strong negative correlations. Consequently, while the GC-MS and SIFT-MS methods exhibited both similarities and differences in phytoncide concentrations, an independent samples t-test, confirming no statistically significant differences between the two methods, suggests the suitability of adopting SIFT-MS over GC-MS for phytoncide collection and analysis in forest environments. Nevertheless, this study contributes to the literature by comparing outdoor phytoncide levels using the GC-MS and SIFT-MS methodologies. These findings, which show that the methods are closely aligned, can guide future researchers in considering SIFT-MS equipment for phytoncide studies, offering a more accessible and efficient option with real-time capabilities.
... More benefits include improved immune function by increasing the effectiveness of natural killer cells and white blood cells (Li & Kawada, 2011;Li et al., 2008;Li et al., 2006); better cognitive and motor development for children by encouraging curiosity, physical activity, and self-reliance (Kellert, 2002;Louv, 2005); a sense of calmness by reducing anxiety and soothing all the senses (Bratman et al., 2015;Maas & Verheij, 2009;Song et al., 2015); better social connectedness and behavior by providing a relaxed natural environment and places conducive to social interaction (De Vries et al., 2013;Williams Goldhagen, 2017); and more happiness by improving general well-being and life satisfaction (Van Herzele & De Vries, 2012;White et al., 2013). ...
Aim:
This review explores the role of purposefully designed and well-integrated therapeutic hospital gardens (THGs) for the benefits of patients, their families, and staff.
Background:
Significant benefits are realized when people are in contact with nature in the city. Although hospital gardens are prevalent and the beneficial effects of nature on health are widely acknowledged, the establishment of a consistent definition for hospital gardens that promote health is vital to attain reliable and quantifiable health outcomes.
Methods:
Twenty-eight peer-reviewed journals were critiqued for the period of 2016-2021 and updated with 12 articles from 2021 to 2023 to analyze and synthesize the latest thinking and development in this emergent field. Subsequently, current books and exemplar practice literature were synthesized with the results of the literature review to produce a working definition of THGs.
Results:
Three themes and 14 subthemes were established showing the interconnectedness of THG definition, user needs and experiences, and the benefits and values of THGs. Two original findings can be established-a need to have a consensus on terminology and to establish design processes. The working definition was produced as a foundational step to guide stakeholders in implementing THGs.
Conclusion:
THGs can play a role in improving well-being when they are purposefully designed and well-integrated in hospital programs and health policy. Hospital CEOs, designers, and healthcare experts can use the findings and working definition to assist the establishment of such health promoting gardens.
... Phytoncides, such as isoprene, α-pinene, and β-pinene, were detected in the forest air [9,17,18,55]. Moreover, phytoncides released from trees significantly increased human NK activity and the intracellular levels of perforin, GrA, and GRN in human NK cells both in vivo [54] and in vitro [90]. ...
Forest bathing was proposed in Japan in 1982 for the purpose of reducing stress and health management, and research on the health promotion and disease prevention effects of forest bathing began in Japan in 2004. Since then, the author’s research team has published many papers and, in 2012, established Forest Medicine as a new preventive medicine. Imagine a new medical science that could let you know how to be more active, more relaxed, healthier, and happier, with reduced stress and a reduced risk of lifestyle-related diseases. This new medical science is Forest Medicine. Forest Medicine studies the effects of forest environments on human health and is a new interdisciplinary science that belongs to the categories of environmental and preventive medicine. On the other hand, more than 10 years have passed since then, and a lot of evidence has been obtained and many articles regarding Forest Medicine have been published. Therefore, in this review, the author proposes a new concept of Forest Medicine, based on the new evidence and published papers, with the psycho-neuro-endocrino-immune network in mind.
... Previous studies have shown that phytoncides increase the number of natural killer (NK) cells, a type of cytotoxic lymphocyte, and improve immune responses (Kim et al., 2018;Li, 2010). Since inhalation of phytoncides has been shown to increase the number of NK cells in the body's circulatory system and help reduce human stress, it has also been shown to be beneficial to humans (Li et al., 2006). Thus, we aimed to evaluate the effects of phytoncides on the immune system of dogs. ...
Background and objective: Phytoncides are volatile and antibacterial organic compounds emitted by plants. In humans, these compounds are known to confer anti-bacterial, antioxidative, anti-inflammatory, immune-response-enhancing, and stress-reducing benefits. However, it remains largely unknown if phytoncides have parallel effects on dogs. Therefore, the aim of this study is to determine if phytoncides exhibit antibacterial activity, initiate an immune response, or alter stress hormone dynamics in dogs.Methods: Phytoncide extracts used in the study were obtained from Hinoki cypress ( Chamaecyparis obtuse ) and Korean red pine ( Pinus densiflora ). To examine the effectiveness of the extracts at initiating and sustaining anti-microbial activity in dogs, we conducted a disc diffusion experiment on bacteria that cause skin diseases in the dog. Furthermore, we evaluated the effects of phytoncides on the immune response and stress hormone levels of dogs by spraying the phytoncide extract on the skin of the beagle twice a day for eight weeks.Results: In this study, we investigated the effectiveness of phytoncides in eliminating bacteria cause skin infections in dogs. Our results confirm that mixed phytoncide extract was more effective than either phytoncide extract alone. After eight weeks, blood was collected from the common carotid artery of the beagle; we then measured the levels of immune response factors and cortisol. We found that with regards to the composition of white blood cells (WBCs), phytoncides significantly increased the proportion of lymphocytes and mononucleotides. They also increased the levels of immunoglobulin G and interferon-γ, while decreasing cortisol levels. Effects on several other immune markers were not significant.Conclusion: We suggest that mixed phytoncide extracts have antibacterial effects in dogs. Additionally, these compounds seem to enhance immunity and reduce stress in dogs.
... In our study, the well-known NK-92 cell line was used to assess the patterns of cell function and metabolite uptake in a simplified allogeneic set-up. This cell line was established in the 1990s and has been used for clinical applications [1], CAR modifications, but also to understand NK cells' behavior in culture [2][3][4][5][6]. NK-92 ′ s high cytotoxicity, due to their lack of almost all inhibitory killer-immunoglobulin-like receptors [KIRs] [7] and their strong resemblance to primary NK cells [6], have made them as a promising candidate for an off-the-shelf cellular immunotherapy for a variety of cancers. ...
Understanding the growth and functionality variation of lymphocytes during expansion is fundamental for
process control and endpoint determination. However, monitoring CQAs along lymphocyte expansion requires
offline cell characterization, hindering timely identification of process deviations and transitions. We developed
a culturing protocol that allowed to investigate day-to-day variation of NK-92 cells’ cytotoxicity against K-562
cells. Replacing 20% of the culture with fresh medium every day while disrupting the formed lymphocyte aggregates,
morphological and functionality changes of the NK-92 cells were induced. Our experiments revealed
that the adaptation to the pseudo-static protocol divided the culture to two distinctive phases with exponential
growth in each. In between, there was an intermittent drop in viability. Significant functionality fluctuations
were observed, despite the regular stimulation strategy. Scale-independent descriptors, such as growth rate, were
calculated for each phase and the whole culture and correlated with cell morphology parameters and functionality.
A novel correlation was found between, the cell size-derived, biomass volume and cytotoxicity that was
stronger during the first phase, but it was apparent throughout the entire culture. This was possible to capture,
only because of the day-to-day monitoring of cytotoxicity. By utilizing the pseudo-static culturing protocol and
the methodology, variables, such as biomass volume, were discovered and by this, we are getting closer to find
performance indicators suitable to monitor CQAs in a straightforward, non-invasive manner.
... . 그 중에서 모노테르펜(monoterpaene, C10H16)과 세스퀴테르펜(sesquiterpene, C15H24)이 대부분을 차지하고 (Zorić et al., 2020;Kim et al., 2022), 특히 모노테르펜 계열인 알파-피넨(α-Pinene)은 피톤치드의 주 요 천연 항생물질로 미생물의 세포 표면에 흡착하여 세포막을 교란 및 파괴함으로써 항균 효과가 있는 것으로 보고되었다 (Dhar et al., 2014;Li et al., 2006). 또한, 진정 작용효과와 수면 개선 효과가 있 으며 (Kawakami et al., 2004;Yang et al., 2016), 그 외에도 고혈압, 항염증 효과가 있다고 알려져 있다 (Orhan et al., 2006). ...
Purpose: This study aims to confirm the physiological activity of cytotoxicity, antioxidant effects, and antibacterial effects of 9 kinds phytoncide extracts were investigated and the possibility of their application as cosmetic materials was studied.Methods: The 9 kinds natural products related to phytoncide extract were selected, extracted, and used as samples. Safety was confirmed through MTT assay, and antioxidant effect through DPPH radical scavenging activity evaluation and antibacterial effect through disc diffusion assay, minimum inhibitory concentration (MIC), and minimum bacteriological concentration (MBC) were evaluated.Results: All 9 kinds phytoncide extracts were confirmed to be safe against Fibroblast cytotoxicity at a concentration of 3.00% or less. The DPPH radical scavenging ability was similar in all phytoncide extracts, and it was confirmed that there was an antioxidant effect. The antibacterial effect did not show strong antibacterial activity against gram-negative bacteria, yeast and fungi as a whole, but it showed excellent antibacterial activity against gram-positive bacteria. Dendranthema zawadskii (Herb.) Tzvelev , Cupressus sempervirens showed antibacterial activity only on gram-positive bacteria. Juniperus chinensis showed excellent antibacterial activity against gram-positive bacteria, yeast. Angelica tenuissima Nakai showed high antibacterial activity against fungi rather than bacteria.Conclusion: These results show that excellent antibacterial and antioxidant effects were confirmed in Dendranthema zawadskii (Herb.) Tzvelev, Cupressus sempervirens , Juniperus chinensis and Angelica tenuissima Nakai at a concentration of 3.00% or less. It is judged that highly likely to be use as a cosmetic material with natural ingredients that replace synthetic preservatives or antioxidants.
... Despite this, steps are beginning to be taken in their study, and despite the lack of knowledge, some evidence is beginning to appear. Metainflammatory mechanisms have been proposed through neuroendocrinological effects of stress and attention, variations in the immune system response through (a) stimulation of a microbiome specific to natural spaces or their interaction with volatile organic compounds emitted by the surrounding vegetation, or in the case of blue spaces, due to the aerosols generated by the tide and the sea breeze [57,58]. Some studies following this trend have found changes in salivary cortisol and an increase in cellular and humoral immunity related to the natural killer cells (NK) [59,60]; (b) intrinsic qualities of green and blue spaces that improve health or well-being (restoration theory) and that have a direct or indirect effect, either through the simple visualization or observation of green or blue spaces; (c) the cushioning and healthy effect associated with green spaces (it cushions the impact of temperature, air pollutants, and noise; (d) the opportunity to engage in physical activity; (e) improve social interactions [61]. ...
Today more than half of the world’s population lives in urban areas. Children spend about 40 h a week in the school environment. Knowing the influence of school exposure to green/blue spaces could improve the children’s health, creating healthier environments and preventing exposure to legal/illegal drugs. This systematic review summarized the main results of published studies on active or passive exposure to green or blue spaces in different domains of child neurodevelopment. In August 2022, five databases were searched and twenty-eight eligible studies were included in the analysis. Cognitive and/or academic performance was the most frequently studied (15/28). Most studies evaluate passive exposure to green/blue spaces (19/28) versus active exposure (9/28). Only three studies addressed the relationship between blue space and neurodevelopment. The main results point toward mixed evidence of a protective relationship between green/blue space exposure and neurodevelopment, especially in improving cognitive/academic performance, attention restoration, behavior, and impulsivity. Renaturalizing school spaces and promoting “greener” capacities for school environmental health could improve children’s neurodevelopment. There was great heterogeneity in methodologies and adjustment for confounding factors across studies. Future research should seek a standardized approach to delivering school environmental health interventions beneficial to children’s development.
... The beneficial effects of visiting a forest derive from the combined stimulation of all senses by specific features of the natural environment [7] whose impact and quantitative assessment have not yet been fully elucidated. Biogenic volatile organic compounds (BVOCs) emitted by plants and soil in the forest atmosphere, and in particular monoterpenes (MTs), as key constituents of BVOCs, have often been suggested as one of the determinants of the interaction between forest ecosystems and human health [17][18][19][20], especially those related to long-lasting effects on the immune system after forest exposure [18,[21][22][23][24][25]. ...
Immersive experiences in green areas, particularly in forests, have long been known to produce beneficial effects for human health. However, the exact determinants and mechanisms leading to healthy outcomes remain to be elucidated. The purpose of this observational cohort study was to investigate whether inhaling plant-emitted biogenic volatile compounds, namely monoterpenes (MTs), can produce specific effects on anxiety symptoms. Data from 505 subjects participating in 39 structured forest therapy sessions at different Italian sites were collected. The air concentration of monoterpenes was measured at each site. STAI state questionnaires were administered before and after the sessions as a measure of anxiety. A propensity score matching analysis was then performed, considering an above-average exposure to inhalable air MTs as the treatment. The estimated effect was −1.28 STAI-S points (95% C.I. −2.51 to −0.06, p = 0.04), indicating that the average effect of exposure to high MT air concentrations during forest therapy sessions was to decrease anxiety symptoms.
... Kato, denominada "shinrin-yoku"(LI, 2010(LI, , 2018, que significa "absorver a atmosfera da floresta". De acordo comLi et al. (2008), phytoncides são exalados durante o processo de evapotranspiração, também típico nas florestas ombrófilas densas de mata atlântica. Acredita-se que a inalação e até a simples precipitação desses elementos possam de alguma forma atuar beneficamente na fisiologia humana.Nesse contexto, com auxílio do guia local, foi possível selecionar indivíduos arbóreos ao longo da trilha do Jequitibá-Cristais, relacionando-os com as propriedades fitoterápicas.Ao longo das trilhas do Jequitibá, foram identificados taxonomicamente inúmeros indivíduos arbóreos com tradição de uso popular de suas essências, sendo comparados com resultados divulgados por inúmeras pesquisas acadêmicas.Ao longo do bordo da trilha foram escolhidas 10 espécies vegetais arbóreas encontradas no complexo de trilhas do Jequitibá-Cristais com o intuito de iniciar um estudo preliminar de suas propriedades fitoterápicas e dos phytoncides produzidos por esses indivíduos arbóreos. ...
... Exposure to the forest environment is associated with greater resistance to future stressors and faster regeneration after a stressful experience, suggesting that forests are important in the prevention of mental and neurodegenerative diseases (Annerstedt et al. 2013). Being in the forest may also strengthen the immune system (Li et al. 2006). People's reliance on access to nature as a source of health during the COVID-19 pandemic was a worldwide phenomenon (Naomi 2020;Weinbrenner et al. 2021). ...
Given the enormous global impact of the COVID-19 pandemic, outbreaks of highly pathogenic avian influenza in Canada, and manifold other zoonotic pathogen activity, there is a pressing need for a deeper understanding of the human-animal-environment interface and the intersecting biological, ecological, and societal factors contributing to the emergence, spread, and impact of zoonotic diseases. We aim to apply a One Health approach to pressing issues related to emerging zoonoses, and propose a functional framework of interconnected but distinct groups of recommendations around strategy and governance, technical leadership (operations), equity, education and research for a One Health approach and Action Plan for Canada. Change is desperately needed, beginning by reorienting our approach to health and recalibrating our perspectives to restore balance with the natural world in a rapid and sustainable fashion. In Canada, a major paradigm shift in how we think about health is required. All of society must recognize the intrinsic value of all living species and the importance of the health of humans, other animals, and ecosystems to health for all.
... A propensity score matching analysis was then performed, considering an aboveaverage exposure to inhalable air MTs as the treatment: the estimated effect was -1.28 STAI-S points (95% C.I. -2.51 to -0.06, p = 0.04), indicating that the average effect of exposure to high MT air concentrations during forest therapy sessions is to decrease anxiety. determinants of the interaction between forest ecosystems and human health [17][18][19][20], especially those related to long-lasting effects on the immune system after forest exposure [18,[21][22][23][24][25]. ...
Immersive experiences in green areas and particularly in forests have long been known to produce beneficial effects for human health. However, the exact determinants and mechanisms leading to healthy outcomes remain to be elucidated. The purpose of this study was to investigate whether inhaling plant-emitted biogenic volatile compounds, namely monoterpenes (MTs), can produce specific effects on anxiety. Data from 505 subjects participating in 39 structured forest therapy sessions in different Italian sites, were collected. Monoterpenes air concentration was measured at each site. STAI State questionnaires were administered before and after the sessions as a measure of anxiety. A propensity score matching analysis was then performed, considering an above-average exposure to inhalable air MTs as the treatment: the estimated effect was -1.28 STAI-S points (95% C.I. -2.51 to -0.06, p = 0.04), indicating that the average effect of exposure to high MT air concentrations during forest therapy sessions is to decrease anxiety.
... El mecanisme de funcionament és a través de la inhalació de compostos orgànics volàtils (phytoncides com el limonè i l'alfa-pinè) que alliberen els arbres de boscos vells i que tenen un efecte estimulant sobre el sistema immunitari, a més de potenciar l'activitat antimicrobiana, reduir el nivell d'estrès del pacient (mesurat en els nivells d'adrenalina en orina i en la tensió arterial) i augmentar els nivells d'adiponectina, proteïna que prevé la diabetes mellitus, malalties cardiovasculars i l'obesitat. Els diferents estudis publicats (Li et al., 2006(Li et al., , 2007 mostren el detall dels mecanismes que entren en funcionament, essent el resultat més destacable l'estimulació de les cèl·lules citocides NK que indueixen l'apoptosi de les cèl·lules tumorals. ...
Evidence of the effect of contact with natural areas on people's health.
Els professionals de la conservació del patrimoni natural, per sort o per desgràcia, ens trobem contínuament amb la ne-cessitat de justificar el perquè de la nostra feina. Al llarg de la història del nostre sector hem anat explorant diferents apro-ximacions a la qüestió: des d'intentar explicar el valor patri-monial d'espècies i hàbitats per se fins a l'intent d'avaluació econòmica dels productes i serveis que els sistemes naturals ens proveeixen. I és que com més urbana es va tornant la nos-tra societat, més cal recordar allò que intuïtivament ja saben els que es dediquen a la producció primària no intensiva: l'espècie humana forma part del sistema natural i com a tal, s'hi troba bé. Des de la Fundació Catalunya-La Pedrera, es van orga-nitzar unes jornades els proppassats 22 i 23 de setembre per donar a conèixer els resultats dels primers estudis científics que busquen evidències de la hipòtesi que el contacte directe amb els sistemes naturals afavoreix la salut de les persones (Fig. 1). Aquest escrit busca ser un recull dels punts que, a criteri del tot subjectiu dels autors, poden ser més rellevants pel nostre sector. Les presentacions realitzades, els ponents que hi van participar i les gravacions de les ponències estan disponibles al web: www.fundaciocatalunya-lapedrera.com/ ca/territori-i-mediambient/salut-i-natura Per començar, voldríem destacar de la primera ponència sobre el projecte europeu PHENOTYPE a càrrec de Mark Nieuwenhuijsen del Centre de Recerca en Epidemiologia Ambiental de Barcelona (CREAL), el recull d'articles cien-tífics que evidencien la percepció intuïtiva que els espais naturals ajuden a reduir l'impacte de malalties a la població o a afavorir la recuperació dels pacients. N'hi ha molts. Desta-quem com a primera cita un article d'Ulrich (1984) publicat a Science on es recollia que els pacients d'un hospital que es recuperaven de cirurgia de vesícula en habitacions amb vis-tes a zones verdes es recuperaven abans i necessitaven menys calmants que els pacients allotjats en habitacions sense vis-tes a zones verdes; a més, tenien millor percepció del tracte rebut pel personal d'infermeria. També que la recuperació davant d'una situació estressant és més ràpida si la persona s'exposa a zones verdes (Ulrich et al., 1991); que les per-sones que caminen habitualment en zones verdes viuen més anys segons un estudi realitzat al Japó (Takano et al., 2002)
... These secondary plant metabolites are used by plants to protect against herbivores and pathogenic micro-organisms, but they have also been shown to exhibit strong anti-inflammatory and antioxidant properties, and can stimulate autophagy [199]. Indeed, an early experiment by Li et al. [200] demonstrated that phytoncides are independently able to influence immune cell function in vitro, therefore suggesting that one benefit of forest bathing may be exposure to beneficial volatile organic compounds often found in relatively higher concentrations in forests [186]. ...
This review shows that relatively simple changes to diet and lifestyle can significantly, and rapidly, reduce the risks associated with coronavirus disease 2019 (COVID-19) in terms of infection risk, severity of disease, and even disease-related mortality. A wide range of interventions including regular exercise, adequate sleep, plant-based diets, maintenance of healthy weight, dietary supplementation, and time in nature have each been shown to have beneficial effects for supporting more positive health outcomes with COVID-19, in addition to promoting better overall health. This paper brings together literature from these areas and presents the argument that non-pharmaceutical approaches should not be overlooked in our response to COVID-19. It is noted that, in several cases, interventions discussed result in risk reductions equivalent to, or even greater than, those associated with currently available vaccines. Where the balance of evidence suggests benefits, and the risk is minimal to none, it is suggested that communicating the power of individual actions to the public becomes morally imperative. Further, many lives could be saved, and many harms from the vaccine mandates avoided, if we were willing to embrace this lifestyle-centred approach in our efforts to deal with COVID-19.
... After the practice, patients reported lower concentrations of cortisol, lower pulse rate, lower blood pressure as well as greater parasympathetic nerve activity, and lower sympathetic nerve activity than in city environments [64]. Various studies suggested that even just the essential oils from plants can stimulate the immunological function of our organisms [65,66], which is fundamental for fetal and maternal wellbeing. Women should be therefore encouraged to "forest bathe" as frequently as they can. ...
Objective: The environmental crisis we are experiencing is becoming a more popular topic of expert discussion and analysis. Human activity and expansion on the planet are exacerbating climate change and global warming, this, together with the increase in plastic production, and general pollution, posing a threat to our resources, supplies, and survival. This research aims to review what is known about the association between pollution and pregnancy and sensitize experts to women’s education towards healthier behaviors. Mechanism: We chose to focus on the effects of the environment on fetal development and maternal health, considering various studies that highlight the potential consequences of exposure to certain environmental stressors. The paper briefly illustrates the probable mechanisms that, starting from cellular and intracellular damage, determined above all by plastics, lead to chronic activation of the immune system in response to danger and, therefore, to epigenetic modifications at the base of diseases in adulthood. Findings in Brief: We describe the effects of the main pollutants on pregnancy, with particular attention to the role of plastic. Finally, we briefly outline some individual possible solutions to this complex problem. Conclusions: In the era of environmental crisis, becoming aware of the mechanisms behind biological damage resulting from exposure to certain pollutants and plastics, especially in a period as sensitive as pregnancy, should be the driving force behind a change of direction. As physicians, this means educating our patients and recommending individual solutions to reduce the impact of contaminants to provide the best possible environment for women’s and children’s health, especially during the delicate period of pregnancy; but the ultimate solution is to drastically reduce global plastic production and pollution, and to recycle the plastic that is needed anyway.
... (Table 2). Volatile compounds emitted by many plants are reported to boost immunity, reduce blood pressure, and alter autonomic activity (Dayawansa et al., 2003;Li et al., 2006;Li et al., 2009;Li 2010). The air around forest areas, mountains, and moving water bodies have more negative air ions, which may enhance mental health and reduce depression (Terman et al., 1998;Theis and Lerdau 2003;Goel et al., 2005). ...
Sacred natural sites are considered part of human beings and communities, consisting of unique medicinal plant species with specific therapeutic properties. Among the sacred trees, Nakshatravan comprises an impressive range of medicinal and aromatic plants, mainly trees, which may help as a source of readily available raw materials from temple premises for traditional medicine. Therefore, the review aims to analyze and compare the medicinal properties and volatile organic compounds (VOCs) of nakshatravan trees, which are associated with 27 nakshatras/constellations used in Vedic tradition since 2nd Century. Various scientific databases, such as Pubmed, Scopus, and Google Scholar, were used. The keywords such as constellation, nakshatravan trees, human health, sacred groves, volatile oil, essential oil, and influence on human diseases were used. The 27 nakshatravan trees belong to 20 families, of which the Moraceae family contributes five trees; Fabaceae, Papilonaceae, and Sapotaceae contribute two trees, whereas the remaining 16 family consists of 1 tree each. There are 92 different medicinal properties, and 132 Volatile Compounds (VCs) and 36 non-volatile compounds (NVCs) noted from 27 trees, which are reported from nakshatravan trees and used for the treatment and prevention of various human diseases. An innovative approach to conserving these plants diversity has been emerging as ‘Star Garden’ comprising imperative medicinal trees with several unique or common medicinal properties. This approach will facilitate establishing and maintaining important, unique medicinal tree species. In the present study, we have analyzed common and unique medicinal properties, volatile and non-volatile compounds of 27 nakshatravan trees, and their potential pharmacological values.
... These studies have clearly shown that forest bathing can benefit human immune function. Studies have also speculated that phytoncides released by trees may be partly responsible for the increased NK activity [12,13,[30][31][32][33][34]. , also examined the relationship between forest cover rate and cancer mortality and revealed significant negative correlations between forest cover rates of all prefectures in Japan and the mortality due to lung, breast, and uterine cancer in women and prostate, kidney, and colon cancer in men [35]. ...
Forests have provided support for human health and survival since ancient times. With improved public awareness of health issues and the importance of forest ecological functions, forest therapy has gradually gained momentum. Forest therapies have been applied around the world as preventive and alternative therapies to promote human health. As a safe, side-effect-free, low-cost, preventive, and alternative therapy, forest therapy has been scientifically proven to promote physical and mental health in humans. However, the forest therapy service system is still underdeveloped, and forest therapy has not become a mainstream part of clinical medical treatment methods in most countries worldwide. Therefore, in order to better present the development path and current situation of forest therapy in different countries and provide guidance for how other countries can develop similar interventions and clinical sites to base these activities, this study uses Germany, Japan, and China as examples to systematically tease out how forest therapy has developed and the status of forest therapy services in different countries, as well as the health benefits of forest therapy. Furthermore, the key components and traditional cultural and socioeconomic backgrounds related to forest therapy are discussed. Finally, based on published empirical research, we believe that forest therapy can be a solution to public health problems thanks to its multiple, medically proven health benefits. Forest therapy facilitates the return of people to the forest and nature to achieve health and well-being effects. However, there is a need for more research on the mechanisms (such as the immune system, endocrine system, nervous system, etc.) underlying forest therapy’s effectiveness, which should include strengthened collaborations between disciplines. In addition, the role of forest therapy services in promoting human health needs to be emphasized.
... These results suggest that chlorpyrifos-methyl generally affects mechanisms associated with detoxification, cytolytic capacity and redox signaling in cod leukocytes. It has been reported that organophosphorus pesticides like chlorpyrifos-methyl diminish natural killer cells and cytotoxic activities in aquatic and human models through different and indirect mechanisms [53][54][55]. Also reported, organophosphorus pesticides induced apoptosis in cultured human lymphocytes of peripheral blood [56] and chlorpyrifos-methyl induced apoptosis and increased apoptotic gene casp3 in the human monocyte cellular line U937 [57]. ...
Inclusion of new environmental toxicants increase with the amount of plant ingredients substituting marine proteins and oils in feed for farmed Atlantic salmon (Salma salar). Agricultural pesticides like chlorpyrifos-methyl, present in commercial salmon feeds, may affect salmon immune and detoxification responses. Atlantic cod (Gadus morhua), surrounding the net pens, grazing on feces and uneaten pellets may be affected accordingly. The aim of this study was to analyze transcription responses in Atlantic cod head kidney tissue and isolated leukocytes following dietary chlorpyrifos-methyl inclusions and possible interactions with proinflammatory signals. Head kidney tissues and leukocytes were isolated from cod fed diets contaminated with chlorpyrifos-methyl (0.5 mg/kg, 2.4 mg/kg, 23.2 mg/kg) for 30 days. The isolated leukocytes were further challenged with bacteria (lipopolysaccharide (LPS), virus (polyinosinic acid:polycytidylic acid (PIC) mimic and l-arginine, an immuno-modulating amino acid, in vitro.
The LPS-induced transcription of the interleukin genes il-1β, il-6, il-8 increased in leukocytes isolated from cod fed chlorpyrifos-methyl 23.2 mg/kg, compared to cod fed the control diet, indicating increased inflammation. Transcriptional levels of carnitine palmitoyl transferase (cpt1a), aryl hydrogen receptor (ahr) and catalase (cat) were all reduced by dietary inclusions of chlorpyrifos-methyl in the leukocytes. The findings suggests that dietary chlorpyrifos-methyl exposure impair inflammation, detoxification and redox signaling in cod leukocytes.
... Finally, it has recently been discovered that the reduction in stress and improvements to the immune system produced by forest visits can be replicated when evergreen oils are removed from trees, aerosolized, and infused in interior spaces [77]. The essential oils emitted by evergreen trees are associated with improvements to the immune system and the production of natural killer cells [78,79]. These effects could be long-term but vary based on gender, with immune functions increased for up to 30 days in men and only seven in women [80]. ...
In recent years, work-related stress has grown exponentially and the negative impact that this condition has on people’s health is considerable. The effects of work-related stress can be distinguished in those that affect workers (e.g., depression and anxiety) and those that affect the company (e.g., absenteeism and productivity). It is possible to distinguish two types of prevention interventions. Individual interventions aim at promoting coping and individual resilience strategies with the aim of modifying cognitive assessments of the potential stressor, thus reducing its negative impact on health. Mindfulness techniques have been found to be effective stress management tools that are also useful in dealing with stressful events in the workplace. Organizational interventions modify the risk factors connected to the context and content of the work. It was found that a restorative workplace (i.e., with natural elements) reduces stress and fatigue, improving work performance. Furthermore, practicing mindfulness in nature helps to improve the feeling of wellbeing and to relieve stress. In this paper, we review the role of mindfulness-based practices and of contact with nature in coping with stressful situations at work, and we propose a model of coping with work-related stress by using mindfulness in nature-based practices.
... Essential oils from different coniferous species and specific terpenes: α-pinene, 1,8-cineole, and d-limonene were used to examine their impact on NK cells. It was concluded that these compounds significantly increased and even restored the lost activity of NK cells [46]. Further on, these findings were confirmed within in vivo experiments in the forest [47] and afterward in unnatural environments where participants were exposed to inhaling the essential oils of previously used conifer species [48]. ...
Numerous medical studies have shown the positive effects of forests on different aspects of human health. This study deals with the content of major terpenes in dominant coniferous species in Tara National Park, Serbia, in order to explore the potential for the development of a novel health tourism programme based on forest therapy. Main terpenes were analysed using a headspace-sampling technique coupled with gas-chromatography-mass spectrometry (Head-space-GC/MS). Needles of fir and spruce growing in the vicinity of hiking trails were investigated for possibilities to perform such therapy. Major detected terpenes were α-cadinol and spathulenol previously described as antiviral, antitumor, antimicrobial and immunomodulatory agents. The results of the study were favourable and worked well with the existing walking infrastructure in the observed area of the Tara Mountain, as they act as invaluable resources for designing the structured forest bathing walks. The study not only adds to the knowledge in the environmental and public health realm but also to tourism and sustainability studies.
... They are volatile chemicals emitted by plants to defend against viruses, bacteria, saccharomyces, molds, and protozoans [69] or to prevent decay and herbivore attacks. Phytoncides also exhibit other beneficial effects, such as anti-microbial, antibacterial [70], anti-fungal, anti-inflammatory, anti-stress, analgesic, and anti-spoilage activities, and they can be used as food preservatives [36,[71][72][73][74][75][76][77][78][79][80][81][82]. They also exhibit anti-mycoplasmal activity [83], anti-larvicidal activity against malaria [84,85] and dengue [86], anti-septic activity, and anthelminthic activity; in addition, they facilitate wound healing [87], can act as cholesterol inhibitors [88], can enhance sleep [89][90][91], and even enhance bacterial susceptibility to antibiotics [92,93]. ...
Chemical compounds from plants have been used as a medicinal source for various diseases. Aromachology is a unique field that studies the olfactory effects after inhaling aromatic compounds. Aromatherapy is a complementary treatment methodology involving the use of essential oils containing phytoncides and other volatile organic compounds for various physical and mental illnesses. Phytoncides possess an inherent medicinal property. Their health benefits range from treating stress, immunosuppression, blood pressure, respiratory diseases, anxiety, and pain to anti-microbial, anti-larvicidal, antiseptic , anti-cancer effects, etc. Recent advancements in aromatherapy include forest bathing or forest therapy. The inhalation of phytoncide-rich forest air has been proven to reduce stress-induced immunosuppression, normalize immune function and neuroendocrine hormone levels, and, thus, restore physiological and psychological health. The intricate mechanisms related to how aroma converts into olfactory signals and how the olfactory signals relieve physical and mental illness still pose enormous questions and are the subject of ongoing research. Aroma-therapy using the aroma of essential oils/phytoncides could be more innovative and attractive to patients. Moreover, with fewer side effects, this field might be recognized as a new field of complementary medicine in alleviating some forms of physical and mental distress. Essential oils are important assets in aromatherapy, cosmetics, and food preservatives. The use of essential oils as an aromatherapeutic agent is widespread. Detailed reports on the effects of EOs in aromatherapy and their pharmacological effects are required to uncover its complete biological mechanism. This review is about the evolution of research related to phytoncides containing EOs in treating various ailments and provides comprehensive details from complementary medicine.
... Forest air contains less dust and gas pollutants, is richer in oxygen, and saturated with essential oils produced by plants (Nowak et al., 2014). The oils also include substances with antibacterial properties comparable to those of antibiotics -phytoncides (Li et al., 2006(Li et al., , 2009. Moreover, daily and annual changes in atmospheric conditions take a milder course, and noise pollution is replaced by the sounds of nature. ...
The largest areas in 23 Polish National Parks are occupied by forests. They include the Świętokrzyski, Roztoczański, Białowieski, and Kampinoski National Parks, where forests cover from 75 to 95% of their area. The recreational layer bioclimate occurring in the forest areas of these parks were investigated. The forest microclimate considerably differs from that which occurs in non−forest areas. Moreover, different forest communities have a different effect on the human organism. The primary objective of the study is a comparative analysis the recreational bioclimate of forest communities along tourist trails in the Białowieski, Świętokrzyski, Kampinoski, and Roztoczański National Parks, with consideration of their health benefits. The forest communities of the analysed parks are dominated by forests with a favourable bioclimate: 62−87%, with the exception of BNP, where they occupy only 11% of the area. Communities with an unfavourable bioclimate cover 22% and 15% of BNP and KNP; in the remaining two parks they cover <5% of the forests. In three of the four national parks analysed, a large majority of tourist trails run through communities with favourable bioclimatic conditions (90% in SNP, 77% in the RNP, and 73% in the KNP), with the exception of BNP (19%). Unfavourable bioclimates are only found on BNP (12%) and KNP (3%) trails. Statistical analysis shows a similarity between the analysed parks in terms of the recreational bioclimate occurring on tourist trails, with the exception of the Białowieski National Park, which is statistically different from the others.
... During their life activity, plants produce volatile organic compounds, phytoncides, protecting themselves from diseases. Phytoncides are bactericidal, protistocidal, and fungicidal substances produced by higher and lower plant organisms for protection and healing purposes (Tokin, 1951;Li, 2006). Nature-based tourism accounts for 7% of all international travel worldwide (Li et al., 2010;Herman et al., 2019). ...
The article presents the prospects for the development of natural and recreational activities in the field of medical and health tourism within the ribbon pine forest, located in the southern outskirts of the West Siberian dry steppe lowland. The purpose of the study is to assess the biological and geographical potential of the forest landscape for the development of recreational areas. This is especially true for the Northern region of Kazakhstan, since industry is developed on the territory, it is characterized by technogenesis. Research methods include field reconnaissance, cartographic modeling using GIS technologies, and laboratory experiments to determine the phytoncide activity of the biological material of trees – Scots pine – collected at different intervals of the day. The results of the study are statistical data on laboratory research. For convenience, they are presented in the form of cartographic material, built based on spatial data of the territory. The paper considers and addresses the ecosystem’s natural potential and the recreational infrastructure of the studied object.
... The health benefits of nature have been identified as one of many essential and life-supporting goods that nature provide to humanity, namely ecosystem services [17,18]. Evidence suggests that nature exposure benefits mental health [19][20][21][22][23][24][25], physical health [26][27][28][29] and immune function [30][31][32]. ...
Exposure to nature has been suggested to promote immigrants’ health and facilitate adaptation. This review summarizes previous research focusing on the relationship between nature and immigrants’ integration, wellbeing and physical activity. A search strategy was developed and adapted to seven databases. After removing duplicates, 4861 records were screened, 81 met inclusion criteria. Community gardens and urban parks were the most studied environments. In these settings, embodied experiences (the interactive processes of sensing and cognition) can foster new memories that facilitate adaptation and attachment to new natural environments. Social interaction and reconnecting with pre-migration experiences through specific use patterns can promote cultural continuation, sense of belonging and wellbeing. Other health benefits such as physical activity, disease management and improved nutrition were less frequently studied. Barriers to participation and recommendations for research and practice were also identified. Use of stronger study designs and greater inclusion of immigrant groups in research, design and evaluation of nature-based initiatives is needed.
... Breathing in the forest's 'volatile' substances can help to reduce stress or enhance rehabilitation and concentration (Hansen et al., 2017;Park, Tsunetsugu, Kasetani, Kagawa, & Miyazaki, 2010). The phytoncides, aromatic molecules released by trees, prompt our bodies to boost the natural killer (NK) cells that attack infections and guard against tumours (Li, 2010;Li et al., 2006). It has been argued that forest bathing can prevent illnesses caused by stress, burn-out and depression, as well as help to establish personal and community identity, social activity, and social participation (Morton, Ferguson, & Baty, 2015). ...
In the troubled times in which we currently live, the tourism industry has called into question a need for more responsible social practices and more mindful utilisation of natural environments. The Japanese practice of shinrin-yoku, or forest bathing, has not only become a new wellness trend, but also a great potential for deeply immersive tourist experiences. While there is a wealth of studies examining the positive effects of forest bathing focussing principally on its medical benefits, this qualitative study extends these debates through documenting lived experiences of forest bathers. In so doing forest bathing suggests its latent potential to offer a profoundly mindful experience, and aims to situate this practice more prominently within the tourism discourse.
... A number of studies [1,7,8,38,48,49] reported that volatile substances (phytoncides) extracted from trees have a positive effect on immune function, supporting the idea that a forest's environmental factors play an instrumental role in improving immune function. An in vitro study indicated that certain volatile tree chemicals, called phytoncides, increase the activation of NK cells and intracellular anti-cancer molecules [50]. This assertion is supported by several studies in animals [51,52] and humans [53], suggesting that fragrances from trees can reverse stress-induced immunosuppression, and normalize immune function and neuroendocrine hormone levels. ...
We conducted a systematic review of the effects of a forest therapy program on adults’ immune function. We used PICO-SD (participants, interventions, comparisons, outcomes, study design) to identify key items. The participants were adults over the age of 18 and the intervention was forest therapy. Our comparisons included studies that comparatively analyzed urban groups or groups that did not participate in forest therapy intervention. Cases without control groups were also included. Immunological outcome measures were included in measuring intervention outcomes. All experimental studies, such as randomized controlled trials (RCTs), non-equivalent control group designs (non-RCTs), and one-group pretest-posttest design were included in the study design. A total of 13 studies were included for comparison. Forest therapy programs were divided into lodging-type and session-type programs. The representative measures for evaluating the effects of immune function were the number of NK cells, the cytotoxic activity of NK cells, and cytotoxic effector molecules. Most studies reported improvement in these measures when comparing values after intervention with values before the forest therapy intervention. Therefore, forest therapy has been found to be effective in improving immune function. More RCT studies on the effects of forest therapy on immune function are necessary.
... Several studies have demonstrated a beneficial effect of forest therapy on human's weakened immune function (Li, 2010;Li et al., 2007;Lyu et al., 2019). These effects might be due to plant-derived phytoncides, which are antimicrobial volatile organic compounds that have been shown to reduce blood pressure, alter autonomic activity, and boost immune function by increasing the concentrations and activity of natural killer (NK) cells, among other effects (Komori et al., 1995;Li et al., 2006). ...
This study examined the associations between green spaces and one–years' worth of SARS–CoV–2 infection rates across all 3,108 counties in the contiguous United States after controlling for multiple categories of confounding factors. We found green spaces at the county level have a significant negative association with infection rates. Among all types of green spaces, forest yields the most consistent and strongest negative association. Sensitivity analyses confirmed the negative association of forest across five urbanicity levels, and the strength of the association increases as disease incidence increases across five time periods. Although forest located in moderately urbanized counties yields the strongest association, the negative pattern of significant associations holds across all five urbanicity levels. A population–weighted analysis revealed that proximity to forest within a moderate walking distance (≤ 1.0–1.4 km) may provide the greatest protection against the risk of infection.
... In addition, Stanhope, et al. [14] proposed other potential reasons for pain relief in a short-term greenspace exposure. For instance, phytoncides may influence the human immune system, enhance natural killer cells' activity and treat some types of pain [51,52]. ...
Reducing the burden of pain via greenspace exposure is a rising research topic. However, insufficient evidence has been found in relation to the environmental effect itself. Residential greenspace, as a convenient but limited natural environment for urban dwellers, has benefits and services yet to be discovered. Therefore, the current study recruited 24 young adults to evaluate the effects of physical visit to, or image viewing of, residential greenspace on pain perception and related psychophysiological outcomes, via simulated pain. Pain threshold and tolerance were recorded via the level of pain stimuli, and pain intensity was evaluated using the Visual Analog Scale (VAS). The state scale of the State–Trait Anxiety Inventory (STAI-S) and two adjective pairs were employed to measure the state anxiety and subjective stress, respectively. Meanwhile, heart rate (HR), heart rate variability (HRV), and blood pressure (BP) were measured to investigate physiological responses. Besides, Scenic Beauty Estimation (SBE) was also employed to assess participants’ preference regarding the experimental environments. The results revealed that visiting the greenspace significantly increased the pain threshold and tolerance, while no significant effect was observed for image viewing. On the other hand, no significant difference was observed in pain-related psychophysiological indices between the experimental settings, but significantly negative associations were found between the scores of SBE and subjective stress and state anxiety. In conclusion, the current study brings experimental evidence of improving pain experience via residential greenspace exposure, while the related psychophysiological benefits require further investigation.
It has long been known that the forest, as a "feel-good space," has a positive effect on human well-being. In recent years, medical studies have also been conducted on this subject. However, there are only a few studies with a sufficient number of cases and valid statistics.
The article describes the various health effects of forest visits on humans, such as physiological and psychological changes, although the mechanisms of action are often still unclear. The field of forest and health research is still in its infancy. A cooperation between the chairs "Forest and Environmental Policy" (TUM) and "Public Health and Health Services Research (IBE)" (LMU) will deal intensively with this topic in the coming years.
This article argues for a mutation in how mental health is conceived in the early twenty-first century. In this mutation, physical environments, in the form of homes, workplaces, and streetscapes, are understood as central to the production and maintenance of good mental health. Much writing on this topic has taken place within a rhetorical division between stereotypically urban buildings or spaces (tower blocks, for example), which are said to be harmful to the human mind, and idealized rural or green spaces, such as parks or small hamlets, understood to be psychologically restorative. This discourse, which has its roots in both cultural and scientific developments, has rendered mental disorder as, at least in part, a spatial problem—which is to say, as a problem that might be both understood through but also treated by spatial practices. The goal of the article is to establish the ground of this claim and to make some of its epistemic roots visible. The article begins with an ethnographic account of a contemporary intellectual movement aimed at populating urban spaces with trees in the name of global mental health. Then the discussion turns to a series of critical developments in the psychological and neurobiological sciences—the article demonstrates how these, in turn, are efflorescing into new links between the architectural and psychological sciences. The article shows how this scientific discussion is paralleled by developments in urban planning—Ebenezer Howard's program of the early twentieth century, set out in Garden Cities of To-Morrow, is taken as exemplary here. The article ends with a reading of Clive Barker's 1985 short story “The Forbidden” and of the film Candyman, which it gave rise to, whose shared sense of horror at the visceral consequences of failed urban experiments, I argue, should be read as a critical inflection point for the contemporary relationship between psychology and architecture.
Die Ökopsychosomatik beschreibt die Wirkung von stofflichen sowie nicht stofflichen Stimulanzien aus Ökosystemen auf die psychische und somatische Gesundheit des Menschen. Sie erforscht die pathogenen und salutogenen Umwelt- und Natureinflüsse, um die daraus gewonnenen Erkenntnisse für die öffentliche Gesundheit sowie für die Therapie von Krankheitszuständen nutzbar zu machen. Im ökopsychosomatischen Paradigma wird der menschliche Organismus als eingebunden in einen evolutionsbedingten Funktionskreis mit seinen natürlichen Lebensräumen betrachtet. Der Mensch ist Teil der Biodiversität. Nicht nur Umweltschadstoffe wirken sich ungünstig auf Gesundheit und Genesungsaussichten aus, sondern auch die Durchbrechung des Funktionskreises durch Trennung von den Einflüssen intakter Ökosysteme. Die „Waldmedizin“ ist als evidenzbasiertes Beispiel der angewandten Ökopsychosomatik und Ökoimmunologie zu betrachten. Der Artikel gibt einen Überblick über das interdisziplinäre Feld der Ökopsychosomatik und Ökoimmunologie.
Shinrin-Yoku describes “bathing in the atmosphere of the forest”. This chapter is about the atmosphere of the forest. It is based on the special climatic factors of forests and their exchange with the environment and the overall atmosphere. We perceive and process the forest atmosphere with all our senses, which includes the structure of the forest and its aesthetics. All these individual elements of the forest atmosphere have concrete health-promoting or even therapeutic effects, which are also demonstrated.
W toczonych od wielu lat dyskusjach na temat roli lasów w bilansie węglowym Biosfery wysuwano argumenty odnoszące się do różnych okresów czasu, od dziesięcioleci po tysiąclecia. Teraz perspektywa czasowa, przynajmniej w Europie, została skonkretyzowana do trzech dziesięcioleci. Nie ma już zatem wielkiego znaczenia rozpatrywanie problemu, na ile stuleci pozostanie związany w biomasie dwutlenek węgla; ważne jest, czy pozostanie tam przez najbliższe dziesięciolecia, oraz ile go tam będzie. Stawia to w innym świetle argumenty odnoszące się do tego, czy dla poprawy bilansu węglowego w skali Biosfery lepiej jest pozostawiać stare lasy bez ingerencji, czy też może lepiej wycinać je i zastępować młodymi? Wycinanie starych lasów po to, żeby poprawić bilans węglowy, nie ma sensu w 30-letniej perspektywie. Młode lasy pochłoną to, co zostało wyemitowane przy wycinaniu starych, nie wcześniej niż za 50-70 lat, a i to przy założeniu, że duża część drewna pozyskanego przy wycinaniu starych lasów zostanie wbudowana w produkty o długim czasie trwania. Należy też pamiętać o tym, że lasy, przede wszystkim te o cechach naturalnych, pełnią kluczową rolę w utrzymaniu globalnej różnorodności biologicznej. Różnorodność biologiczna lasów jest rezultatem procesów ewolucyjnych toczących się w nich przez tysiące, a nieraz miliony lat, pod wpływem klimatu, ognia, konkurencji i zaburzeń. Tak zróżnicowane biologicznie układy stwarzają organizmom szansę na adaptację do stale zmieniających się warunków środowiskowych i zapewniają ciągłość procesów ekologicznych, gwarantujących trwałość lasów i zapewniających korzyści człowiekowi. Bogate w gatunki, zróżnicowane strukturalnie lasy nabierają więc szczególnie dużego znaczenia w dobie kryzysu klimatycznego, albowiem nie tylko efektywnie kumulują węgiel, ale też dają możliwość przetrwania gatunkom najlepiej adaptującym się do zmian klimatu i nasilających się wraz z nimi zaburzeń. Wraz ze wzrostem urbanizacji i świadomości ekologicznej społeczeństwa z roku na rok rośnie również znaczenie tych funkcji lasu, które nie wiążą się bezpośrednio z materialnymi korzyściami. Wśród nich są m. in. magazynowanie i cyrkulacja wody, regulacja klimatu, regulacja populacji szkodników i chorób, czy też niezbędne dla zdrowia psychicznego duchowe, rekreacyjne i intelektualne interakcje z przyrodą. Znaczenie tych ostatnich jest jeszcze słabo rozpoznane, ale wydaje się, że odgrywają dużą rolę zwłaszcza w otoczeniu większych miast oraz w regionach uznawanych za ostoje naturalności. Gospodarując w lesie, kształtując jego strukturę i skład gatunkowy, wpływamy zarówno na liczbę jak i na intensywność produkcyjnych i pozaprodukcyjnych funkcji lasu. Oczywiście potrzebujemy i będziemy potrzebować drewna, gdyż jest ono bardzo ważnym surowcem. Lepiej jednak nie pozyskiwać go w starych lasach, tylko w drzewostanach młodszych, a zwłaszcza plantacjach zakładanych na terenach obecnie bezleśnych. Plany KE zmierzające do objęcia ochroną 30% obszarów, w tym 10% ochroną ścisłą są milowym krokiem w kierunku efektywnej ochrony ekosystemów leśnych Europy, w tym najlepiej zachowanych, starych lasów. Potrzebujemy nowego podejścia do zarządzania lasami, które zminimalizuje rosnącą liczbę konfliktów na styku gospodarki leśnej i społeczeństwa.
Environmental neuroscience is a field which uses multiple scales of analysis to elucidate the ways in which the physical environment interacts with neural processing to affect behavior. One environment that is heavily studied by environmental neuroscientists is the natural environment and how interacting with more natural environments (e.g., a city park) may benefit psychological functioning. This multidisciplinary environmental neuroscience approach examines processes and factors that vary across temporal and spatial scales. Most research studies examining the effects of interacting with natural environments on individuals’ neural processing and behavior fall into what we term meso-scale studies, which consist of real or simulated nature exposure on the order of minutes to hours. These are typically laboratory studies which attempt to quantify the effects of nature in an experimental setting. Macro-scale studies examine the effects of nature/green space exposure on people across large populations (e.g., a city) over long durations (e.g., on the order of years). These studies are typically observational but speak to the ecological validity of the meso-scale studies. Micro-scale studies tend to examine the specific elements of natural environments that may lead to the psychological benefits of interacting with nature, such as the low-level visual and acoustic features of nature and how perceiving those features may lead to cognitive benefits. Though immense progress has already been made in these domains, we propose that rapid advancements will be made through the increased use of methods that can span temporal and spatial scales and with more rigorous neuroimaging research, which may identify the neural mechanisms which drive these behavioral effects. We conclude with a brief discussion for how adopting an environmental neuroscience perspective can be of value to other fields of research, such as urban planning and environmental conservation.
Mice bearing the experimental murine renal cancer Renca can be successfully treated with some forms of immunotherapy. In the present study, we have investigated the molecular pathways used by NK and T cells to lyse Renca cells. Renca cells normally express low levels of Fas that can be substantially enhanced by either IFN-γ or TNF-α, and the combination of IFN-γ + TNF-α synergistically enhances cell-surface Fas expression. In addition, cells pretreated with IFN-γ and TNF-α are sensitive to lysis mediated by Fas ligand (FasL)-expressing hybridomas (dllS), cross-linking of anti-Fas Abs or soluble Fas (FasL). Lysis via Fas occurs by apoptosis, since Renca shows all the typical characteristics of apoptosis. No changes in levels of bcl-2 were observed after cytokine treatments. We also examined cell-mediated cytotoxic effects using activated NK cells and T cells from gld FasL-deficient mice, and perforin-deficient mice, as well as wild-type C57BL/6 and BALB/c mice. Interestingly, the granule-mediated pathway predominated in killing of Renca by activated NK cells, while the Fas/FasL pathway contributed significantly to cell-mediated killing of Renca by activated T cells. These results suggest that killing of Renca tumor cells by immune effector cells can occur by both granule and Fas-mediated cytotoxicity. However, for the Fas-mediated pathway to function, cell surface levels of Fas need to be increased beyond a critical threshold level by proinflammatory cytokines such as IFN-γ and TNF-α.
Using a subtractive hybridization procedure we have constructed a cDNA library enriched for sequences present in functional human T cell lines, but not in human EBV-transformed B cell lines. We have isolated a cDNA clone, AH2-519, representing a novel gene, designated 519. This novel gene is expressed in functional human cytolytic and Th cell lines but not in a variety of other cell lines, including several long-term human T cell tumor lines. The expression of gene 519 is inducible in cultures of normal human PBL using antigenic or mitogenic stimulation. Neither the DNA sequence determined from a full-length cDNA clone overlapping with clone AH2-519 nor the amino acid sequence of its predicted protein product has significant homology to published sequences in the GenBank or NBRF databases. The restricted expression of gene 519 suggests that its gene product is involved in the growth and/or differentiation of normal T cells. The data also show that normal, nontransformed, functional T cells express gene products that can not be readily identified in long-term tumor lines of the same cell lineage.
Two molecular mechanisms of T cell-mediated cytotoxicity, one perforin-based, the other Fas-based, have been demonstrated.
To determine the extent of their contribution to T cell-mediated cytotoxicity, a range of effector cells from normal control
or perforin-deficient mice were tested against a panel of target cells with various levels of Fas expression. All cytotoxicity
observed was due to either of these mechanisms, and no third mechanism was detected. Thus, the perforin- and Fas-based mechanisms
may account for all T cell-mediated cytotoxicity in short-term in vitro assays.
Cytolytic T lymphocytes (CTLs) kill intracellular pathogens by a granule-dependent mechanism. Granulysin, a protein found
in granules of CTLs, reduced the viability of a broad spectrum of pathogenic bacteria, fungi, and parasites in vitro. Granulysin
directly killed extracellularMycobacterium tuberculosis, altering the membrane integrity of the bacillus, and, in combination with perforin, decreased the viability of intracellular
M. tuberculosis. The ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute
to immunity against intracellular pathogens.
CTL and NK cells use two distinct cytocidal pathways: 1) perforin and granzyme based and 2) CD95L/CD95 mediated. The former requires perforin expression by the effectors (CTL or NK), whereas the latter requires CD95 (Fas/APO-1) expression by the target. We have investigated how these two factors contribute to tumor immune surveillance by studying the immunity of perforin-deficient mice against the progressor C57BL/6 Lewis lung carcinoma 3LL, which expresses no CD95 when cultured in vitro. Unexpectedly, the results indicated that the perforin-independent CD95L/CD95 pathway of CTL/NK plays a role in acting against D122 and Kb39.5 (39.5) high and low metastatic sublines, respectively, derived from the 3LL tumor. Although no membrane-bound CD95 was detected on cultured D122 and 39. 5 cells, surface CD95 expression on both D122 and 39.5 was considerably up-regulated when the tumors were grown in vivo. A similarly enhanced expression of CD95 was observed with three additional tumors; LF-, BW, and P815, injected into syngeneic and allogeneic mice. The finding of up-regulated CD95 expression on tumor cells placed in vivo suggests that a CD95-based mechanism plays a role in tumor immunity at early stages of tumor growth. Consequently, the progressive down-regulation of CD95 expression during tumor progression may indeed be an escape mechanism as previously reported. Together, these results suggest a role for CD95-dependent, perforin-independent immunity against certain tumors.
The cytotoxic T lymphocyte protease granzyme A induces caspase-independent cell death in which DNA single-strand nicking is
observed instead of oligonucleosomal fragmentation. Granzyme A is a specific tryptase that concentrates in the nucleus of
targeted cells and synergistically enhances DNA fragmentation induced by the caspase activator granzyme B. Here we show that
granzyme A treatment of isolated nuclei enhances DNA accessibility to exogenous endonucleases.In vitro and after cell loading with perforin, GrnA completely degrades histone H1 and cleaves core histones into ∼16-kDa fragments.
Histone digestion provides a mechanism for unfolding compacted chromatin and facilitating endogenous DNase access to DNA during
T cell and natural killer cell granule-mediated apoptosis.
The effects of chiral fragrances (enantiomers of limonene and carvone) on the human autonomic nervous system (ANS) and on self-evaluation were studied in 20 healthy volunteers. Each fragrance was administered to each subject by inhalation using an A–A–B design. Individuals were tested in four separate sessions; in one session one fragrance was administered. ANS parameters recorded were skin temperature, skin conductance, breathing rate, pulse rate, blood oxygen saturation and systolic
as well as diastolic blood pressure. Subjective experience was assessed in terms of mood, calmness and alertness on visual analog scales. In addition, fragrances were rated in terms of pleasantness, intensity and stimulating property. Inhalation of (+)-limonene led to increased systolic blood pressure, subjective alertness and restlessness. Inhalation of (–)-limonene caused an increase in systolic blood pressure but had no effects on psychological parameters. Inhalation of (–)-carvone caused increases in pulse rate, diastolic blood pressure and subjective restlessness. After inhalation of (+)-carvone increased levels of
systolic as well as diastolic blood pressure were observed. Correlational analyses revealed that changes in both ANS parameters and self-evaluation were in part related to subjective evaluation of the odor and suggest that both pharmacological and psychological mechanisms are involved in the observed effects. In conclusion, the present study indicates that: (i) prolonged inhalation of fragrances influences ANS parameters as well as mental and emotional conditions; (ii) effects of fragrances are in part based on subjective evaluation of odor; (iii) chirality of odor molecules seems to be a central factor with respect to the
biological activity of fragrances.
We investigated the effects of fragrance inhalation on sympathetic activity in normal adult subjects using both power spectral analysis of blood pressure fluctuations and measurement of plasma catecholamine levels. Fragrance inhalation of essential oils, such as pepper oil, estragon oil, fennel oil or grapefruit oil, resulted in 1.5- to 2.5-fold increase in relative sympathetic activity, representing low frequency amplitude of systolic blood pressure (SBP-LF amplitude), compared with inhalation of an odorless solvent, triethyl citrate (P<0.05, each). In contrast, fragrance inhalation of rose oil or patchouli oil caused a 40% decrease in relative sympathetic activity (P<0.01, each). Fragrance inhalation of pepper oil induced a 1.7-fold increase in plasma adrenaline concentration compared with the resting state (P = 0.06), while fragrance inhalation of rose oil caused a 30% decrease in adrenaline concentration (P<0.01). Our results indicate that fragrance inhalation of essential oils may modulate sympathetic activity in normal adults.
Granulysin, a molecule present in the granules of CTL and NK cells, is cytolytic against microbes and tumors. Granulysin induces apoptosis of mammalian cells by damaging mitochondria and causing the release of cytochrome c and apoptosis-inducing factor, resulting in DNA fragmentation. Here we show that Ca2+ and K+ channels as well as reactive oxygen species are involved in granulysin-mediated Jurkat cell death. The Ca2+ channel blockers, nickel and econazole, and the K+ channel blockers, tetraethylammonium chloride, apamin, and charybdotoxin, inhibit the granulysin-induced increase in intracellular Ca2+ ([Ca2+](i)), the decrease in intracellular K+, and apoptosis. Thapsigargin, which releases Ca2+ from the endoplasmic reticulum, prevents a subsequent granulysin-induced increase in [Ca2+](i) in Jurkat cells, indicating that the initial increase in [Ca2+](i) is from intracellular stores. The rise in [Ca2+](i) precedes a decrease in intracellular K+, and elevated extracellular K+ prevents granulysin-mediated cell death. In granulysin-treated cells, electron transport is uncoupled, and reactive oxygen species are generated. Finally, an increase in intracellular glutathione protects target cells from granulysin-induced lysis, indicating the importance of the redox state in granulysin-mediated cell death.
Using a subtractive hybridization procedure we have constructed a cDNA library enriched for sequences present in functional human T cell lines, but not in human EBV-transformed B cell lines. We have isolated a cDNA clone, AH2-519, representing a novel gene, designated 519. This novel gene is expressed in functional human cytolytic and Th cell lines but not in a variety of other cell lines, including several long-term human T cell tumor lines. The expression of gene 519 is inducible in cultures of normal human PBL using antigenic or mitogenic stimulation. Neither the DNA sequence determined from a full-length cDNA clone overlapping with clone AH2-519 nor the amino acid sequence of its predicted protein product has significant homology to published sequences in the GenBank or NBRF databases. The restricted expression of gene 519 suggests that its gene product is involved in the growth and/or differentiation of normal T cells. The data also show that normal, nontransformed, functional T cells express gene products that can not be readily identified in long-term tumor lines of the same cell lineage.
More than 5000 passengers on Tokyo subway trains were injured by the nerve gas, sarin and its by-products. Analysis of phosphor-carrying metabolites of sarin and its by-products in urine samples from the victims suggested that they were exposed not only to sarin, but also by-products generated during sarin synthesis, i.e. diisopropyl methylphosphonate (DIMP) and diethyl methylphosphonate (DEMP). We suspected genetic after-effects due to sarin by-products, thus, we checked the frequency of sister chromatid exchange (SCE) and found that SCE was significantly higher in the victims than in a control group, and that DIMP and DEMP significantly induced human lymphocyte SCE in vitro. In the present study, to explore whether DIMP and DEMP, which induced a high frequency of SCE of lymphocytes, also affected the lymphocyte functions, we examined the effect of DIMP and DEMP on splenic natural killer (NK) and splenic cytotoxic T lymphocyte (CTL) activity in mice, and NK activity of human lymphocytes in vitro. We found that DIMP and DEMP significantly inhibited NK and CTL activity in a dose-dependent manner. The inhibition induced by DIMP was stronger than that by DEMP. The effect of DIMP and DEMP on the splenic NK activity of mice was stronger than on the splenic CTL activity, and the human lymphocytes is more sensitive to DIMP and DEMP than the splenocytes of mice.
The aim of this study was to determine the effects of olfactory stimulation on immunological and behavioral states in mice. Anti-SRBC (IgM) plaque forming cell (PFC) count and spontaneous running activity (SRA) were measured to demonstrate the effects of exposure to a given fragrance. The decreased PFC count and thymic involution induced by high pressure stress in mice were recovered after exposing the stressed mice to the fragrance continuously for 4 days after the stress was given. The PFC and SRA also appeared to be maintained at normal levels by oflactory stimulation with the fragrance for 24 hrs after the given stress. The immunological suppression induced by high pressure stress was considered to be caused by the induction and activation of suppressor cells. However, exposure to the fragrance after the stress did not enhance suppressor activity. The restoration of the stress-induced immune suppression by olfactory stimulation was blocked by procain administration onto the olfactory cells.
Perforin is one of the cytolytic factors present in the cytoplasmic granules of mouse cytotoxic T lymphocytes and natural killer cells. We have determined the sequence of the N-terminal amino acids of perforin purified from a mouse natural killer cell line, and, by using oligonucleotide probes corresponding to the amino acid residues, we have identified a complementary DNA encoding perforin from the cDNA library of a mouse cytotoxic T lymphocyte clone. As predicted from the functional similarities between perforin and the ninth component of the serum cytolytic system, complement (C9) (refs 4-8), the deduced primary structure of perforin has homology with C9 at their respective functionally conserved regions. We find that perforin is only expressed in killer cell lines, and not in helper T lymphocytes or other tumour cells tested. Thus we have provided direct molecular evidence that a killer-cell-specific protein evolutionally linked to C9 is involved in cell-mediated cytolysis.
The recent generation of perforin knock-out mice has demonstrated a crucial role for the pore-forming perforin in cytolytic T-lymphocyte (CTL)-mediated cytolysis. Perforin-deficient mice failed to clear lymphocytic choriomeningitis virus in vivo, yet substantial killing activity still remained in perforin-free CTLs in vitro, indicating the presence of (a) further lytic pathway(s). Fas is an apoptosis-signalling receptor molecule on the surface of a number of different cells. Here we report that both perforin-deficient and Fas-ligand-deficient CTLs show impaired lytic activity on all target cells tested. The killing activity was completely abolished when both pathways were inactivated by using target cells from Fas-receptor-deficient lpr mice and perforin-free CTL effector cells. Fas-ligand-based killing activity was triggered upon T-cell receptor occupancy and was directed to the cognate target cell. Thus, two complementary, specific cytotoxic mechanisms are functional in CTLs, one based on the secretion of lytic proteins and one which depends on cell-surface ligand-receptor interaction.
Cytotoxic lymphocytes mediate immunity against viruses and surveillance against neoplastic transformation. They kill target cells by multiple mechanisms, but utilize a pore-forming protein, perforin, and a family of serine proteinases as their principal means of inflicting cell death. Recent studies have demonstrated that perforin and serine proteinases synergistically trigger an endogenous pathway of apoptosis resulting in dissolution of the target cell nuclear membrane and DNA fragmentation. These changes may be secondary to inappropriate activation of p34cdc2 kinase and the subsequent derangement of cell cycle control. As discussed by Mark Smyth and Joseph Trapani, the immediate molecular targets of perforin/granzyme-mediated apoptosis are still unclear, though candidate molecules with homology to cell death gene products from primitive organisms are currently under close scrutiny.
The cell line described here was established for a 50-year-old male patient with rapidly progressive non-Hodgkin's lymphoma whose marrow was diffusely infiltrated with large granular lymphocytes (LGL). Immunophenotyping of marrow blasts and peripheral lymphocytes was positive for CD56, CD2 and CD7, and negative for CD3. Cytotoxicity of peripheral blood mononuclear cells at an effector:target (E:T) cell ratio of 50:1 was 79% against K562 cells and 48% against Daudi cells. To establish the line, cells from the peripheral blood were placed into enriched alpha medium containing 12.5% fetal calf serum, 12.5% horse serum, 10-4 M β-mercaptoethanol and 10-6 M hydrocortisone. Growth of the line (termed NK-92) is dependent on the presence of recombinant IL-2 and a dose as low as 10 U/ml is sufficient to maintain proliferation. Conversely, cells die within 72 h when deprived of IL-2; IL-7 and IL-12 do not maintain long-term growth, although IL-7 induces short-term proliferation measured by 3H-thymidine incorporation. None of the other cytokines tested (IL-1α, IL-6, TNF-α, IFN-α, IFN-γ) supported growth of NK-92 cells which have the following characteristics: surface marker positive for CD2, CD7, CD11a, CD28 CD45, CD54, CD56(bright), surface marker negative for CD1, CD3, CD4, CD5, CD8, CD10, CD14, CD16, CD19, CD20, CD23, CD34, HLA-DR. DNA analysis showed germline configuration for T-cell receptor β and γ genes. CD25 (p55 IL-2 receptor) is expressed on about 50% of all cells when tested at 100 U/ml of IL-2 and its expression correlates inversely with the IL-2 concentration. The p75 IL-2 receptor is expressed on about half of the cells at low density irrespective of the IL-2 concentration. NK-92 cells kill both K562 and Daudi cells very effectively in a 4 h51-chromium release assay (84 and 86% respectively, at an E:T cell ratio of 5:1). The cell line described here thus displays characteristics of activated NK-cells and could be a valuable tool to study their biology.
Perforin-deficient mice have been generated by homologous recombination to determine whether the effects of CD8+ cytolytic T cells and natural killer cells are mediated by pore formation involving perforin. These mice are viable and fertile and have normal numbers of CD8+ T cells and natural killer cells which do not lyse virus-infected or allogeneic fibroblasts or natural killer target cells in vitro. The mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumour cells with reduced efficiency. Perforin is therefore a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis.
In our previous experiments on animals evidence was found that citrus fragrance can restore the stress-induced immunosuppression, suggesting that citrus fragrance may have an effect on restoring the homeostatic balance. Since a dysregulation of the neuroendocrine and immune function is thought to be associated with psychosomatic or psychiatric disorders an attempt was made to restore their mental health by stimulation of one of the sensory systems. Fragrance (citrus was our choice) which comforts through stimulation of the olfactory system was applied to depressive patients. It was given to 12 depressive subjects and the results indicated that the doses of antidepressants necessary for the treatment of depression could be markedly reduced. The treatment with citrus fragrance normalized neuroendocrine hormone levels and immune function and was rather more effective than antidepressants.
The release of cytotoxic granule contents by cytotoxic T lymphocytes triggers apoptotic target cell death. Cytotoxic granules contain a pore-forming protein, perforin, and a group of serine proteases called granzymes. We expressed human granzyme A in bacteria as a proenzyme capable of in vitro activation by enterokinase. The recombinant activated enzyme has catalytic activity against substrates with Arg, preferably, or Lys at the P1 position, comparable to trypsin. An enzymatically inactive recombinant granzyme A, with the active site Ser mutated to Ala, was produced and used with affinity chromatography to identify potential substrates. Two granzyme A-binding cytoplasmic proteins of molecular mass 33 and 44 kDa were isolated and identified by tryptic fragment sequencing as PHAP I and II, ubiquitous putative HLA-associated proteins, previously coisolated by binding to an HLA class II peptide. PHAP II forms an SDS-stable complex with recombinant mutant granzyme A and coprecipitates with it from cytoplasmic extracts. PHAP II, either purified or in cell lysates, is cleaved by the recombinant enzyme at nanomolar concentrations to a 25-kDa fragment. PHAP II begins to be degraded within minutes of initiation of cytotoxic T lymphocyte attack. PHAP I and II are candidate participants in the granzyme A pathway of cell-mediated cytotoxicity.
To study the effects of perfume and phytoncid on GABAA receptors, ionotropic GABAA receptors were expressed in Xenopus oocytes by injecting mRNAs that had been prepared from rat whole brain. Essential oil, perfume and such phytoncid as leaf alcohol, hinokitiol, pinene, eugenol, citronellol and citronellal potentiated the response in the presence of GABA at low concentrations (10 and 30 microM), possibly because they bound to the potentiation-site in GABAA receptors and increased the affinity of GABA to the receptors. Since it is known that the potentiation of GABAA receptors by benzodiazepine, barbiturate, steroids and anesthetics induces the anxiolytic, anticonvulsant and sedative activity or anesthetic effect, these results suggest the possibility that the intake of perfume or phytoncid through the lungs, the skin or the intestines modulates the neural transmission in the brain through ionotropic GABAA receptors and changes the frame of the human mind, as alcohol or tobacco does.
NK-92 is a highly cytotoxic natural killer (NK) tumor cell line that possesses properties that make it an excellent candidate for adoptive cellular immunotherapy. However, the cytotoxicity of NK cells is dependent on cytokines such as interleukin 2 (IL-2). Although NK-92 cells maintain cytotoxicity for a time after withdrawal of IL-2, clinical use will probably require prolonged treatment with fully activated cells to eliminate disease effectively. The ability to support cytotoxic cells with exogenously administered IL-2 is limited by associated toxicity. Therefore, we describe the transfection of the IL-2-dependent NK-92 cell line with human IL-2 (hIL-2) cDNA by particle-mediated gene transfer to create two IL-2-independent variants, NK-92MI and NK-92 CI, and describe their characterization and comparison with parental cells. Both variants were shown to contain, express, and synthesize the hIL-2 cDNA. IL-2 synthesis was higher in NK-92MI cells compared with NK-92CI cells, with no expression in parental cells. Functionally, the cytotoxicity of all three cell lines was similar and coincubation with IL-2-independent variants did not affect hematopoietic progenitor cells. NK-92MI and NK-92CI cells were more radiosensitive than NK-92 cells, with proliferation inhibited at lower radiation doses and increased morality and decreased cytotoxicity compared with parental cells. Data presented here show that we have created by particle-mediated gene transfer two IL-2-independent variants of NK-92 that are identical to parental cells in virtually all respects, including high cytotoxic activity. The nonviral transfection of these cells makes them suitable for clinical applications. These IL-2-independent cells should allow prolonged treatment with fully active natural killer cells without the need for exogenous IL-2 support.
Granulysin is a newly described lytic molecule expressed by CTL and NK cells. Three mRNA (519, 520, and 522) and two protein products of 15 and 9 kDa are encoded by the granulysin gene. Stable transfectants overexpressing the predominate 520 mRNA were generated to determine the protein products originating from the translation of this message. A transfectant of the NK cell tumor YT overexpressed both 15 and 9 kDa proteins while a transfectant of the T cell tumor HuT78 produced mainly 15 kDa granulysin. Thus the 520 mRNA is sufficient for production of both 15 and 9 kDa granulysin. 9 kDa granulysin accumulated via post-translational processing of 15 kDa protein and was present intracellularly but not in the cell culture supernatant, indicating specific retention of the 9 kDa protein. An inhibitor of granule acidification, concanamycin A, blocked the processing of 15 kDa granulysin to the 9 kDa form. A deduced structural difference between the two forms of the protein and a decrease in lytic activity of 9 kDa granulysin at granule pH suggest two mechanisms by which a granulysin expressing cell is protected from autolysis during the biosynthesis of this potentially harmful molecule.
Cytotoxic T lymphocytes (CTL) induce apoptosis by engaging death receptors or by exocytosis of cytolytic granules containing granzyme (Gzm) proteases and perforin. The lamins, which maintain the structural integrity of the nuclear envelope, are cleaved by caspases during caspase-mediated apoptosis. Although death receptor engagement and GzmB activate caspases, CTL also induce apoptosis during caspase blockade. Both GzmA and GzmB directly and efficiently cleave laminB in vitro, in situ in isolated nuclei and in cells loaded with perforin and Gzms, even in the presence of caspase inhibitors. LaminB is cleaved by GzmA at concentrations of 3 nM, but GzmB is 50 times less active. GzmA cuts laminB at R392; GzmB cuts at the caspase VEVD231 site. Characteristic laminB fragments generated by Gzm proteolysis also are observed during CTL lysis, even in the presence of caspase inhibitors or in cells overexpressing bcl-2. Lamins A/C are direct substrates of GzmA, but not GzmB. GzmA and GzmB therefore directly target critical caspase substrates in caspase-resistant cells.
We have previously found that diisopropyl methylphosphonate, an organophosphorus by-product generated during sarin synthesis in the Tokyo sarin disaster, significantly inhibited natural killer (NK) and cytotoxic T lymphocyte (CTL) activities. In the present study, to investigate whether organophosphorus pesticides (OPs) also affect NK and CTL activities, we firstly examined the effect of five OPs on human NK activity, and then the effect of Dimethyl 2,2-dichlorovinyl phosphate (DDVP), an OP on murine splenic NK, CTL and lymphokine-activated killer (LAK), and human LAK activities in vitro. To explore the underlying mechanism of decreased NK activity, we also investigated the effect of 4-(2-aminoethyl) benzenesulfonyl fluoride-HCl (p-ABSF), an inhibitor of serine proteases on NK, LAK and CTL activities, and the effect of DDVP on the activity of granzymes (serine proteases). We found that OPs significantly decreased human NK activity in a dose-dependent manner, but the degree of decrease in NK activity differed among the OPs investigated, and that DDVP significantly decreased NK, LAK and CTL activities in a dose-dependent manner, but the degree of decrease in these activities differed. p-ABSF showed a similar inhibitory pattern to DDVP, and had an additive inhibitory effect with DDVP on NK, LAK and CTL activities. We also found that DDVP significantly inhibited granzyme activity in a dose-dependent manner. These findings indicate that OPs significantly decrease NK, LAK and CTL activities in vitro via granzyme inhibition.
Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells induce target cell death by two main mechanisms, the perforin/granzyme pathway and the Fas-ligand (FasL)/Fas pathway. We have previously found that organophosphorus pesticides significantly inhibit human and murine NK, LAK and CTL activities and that this inhibition is partially mediated by the inhibition of granzymes. We asked here whether organophosphorus pesticides also affect the FasL/Fas pathway by using perforin-knockout (PKO) mice. Thus, we examined the effect that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide has on NK, CTL and LAK activities of PKO mice in vitro using the Fas antigen-positive YAC-1 cell as a target in the present study. We found that DDVP significantly decreased NK, CTL and LAK activities in a dose-dependent manner, and that the CTL and LAK activities of PKO mice were significantly blocked by anti-FasL antibody, suggesting that DDVP and anti-FasL antibody have the same/similar mechanism of inhibiting LAK and CTL activities. We further found that DDVP decreases the expression of Fas antigen on YAC-1 cells, and the expression of FasL on LAK cells in a dose-dependent manner, respectively. Taken together, these findings indicate that the DDVP-induced inhibition of NK, LAK and CTL activities in PKO mice is mediated by the impairment of the FasL/Fas pathway.
1. Phytoncides are volatile substances released mainly from trees. We studied whether phytoncides can reduce stress responses in stroke-prone spontaneously hypertensive rats (SHRSP).
2. Under the restraint stress, SHRSP exposed to phytoncides showed lower blood pressure than those without the exposure (186.8 ± 3.9 vs 207.7 ± 3.4 mmHg, respectively, P < 0.01 by Student's t-test).
3. Consistent with the observation above, the plasma concentration of catecholamines under the restraint stress was lower in the phytoncides group than in the control group.
4. Based on these results, we concluded that phytoncides reduced the cardiovascular response to restraint stress in SHRSP.
Natural killer (NK), lymphokine-activated killer (LAK) and cytotoxic T lymphocyte (CTL) cells kill target cells by the directed release of cytolytic granules that contain perforin, granzymes and granulysin. We previously have found that dimethyl 2,2-dichlorovinyl phosphate (DDVP), an organophosphorus pesticide significantly inhibited NK, LAK and CTL activities via the inhibition of granzyme activity. To further explore the mechanism of organophosphorus pesticide-induced inhibition of cell-mediated cytolysis, we asked here whether organophosphorus pesticides affect the expression of perforin, granzyme and granulysin in NK cells. We used NK-92CI cell, an interleukin-2 (IL-2) independent human NK cell line. We confirmed that NK-92CI cells express CD56 surface marker, perforin, granzyme A and granulysin by flow cytometry and immunofluorescence microscope, and that it is highly cytotoxic to K562 cells in chromium release assay. We found that DDVP significantly decreases the expression of perforin, granzyme A and granulysin in NK-92CI cells in a dose-dependent manner. Immunocytochemical results showed that DDVP significantly decreases perforin, granzyme A and granulysin positive granules in NK-92CI cell, which may be due to the degranulation. We also found that DDVP have a modest, but a significant inhibitory effect on the transcription of mRNA of perforin, granzyme A and granulysin.
Granulysin is a cytolytic granule protein of natural killer (NK) cells and cytotoxic T lymphocytes (CTL) with a broad range of antimicrobial and tumoricidal activities. Two molecular forms of granulysin, the 15-kDa precursor and 9-kDa mature form, are produced in these cells. In this study, we developed monoclonal antibodies against granulysin and found that the 15-kDa granulysin is spontaneously secreted by peripheral blood NK and T cells via a non-granule exocytotic pathway. When NK cells killed the target cells, the released granulysin levels in culture supernatants significantly increased through the granule exocytosis. The granulysin protein was found in the sera of healthy individuals at an average concentration of 3.7 +/- 3.2 ng/ml (age 0-99 years, n=244). The serum levels of granulysin were transiently highly elevated among patients with acute viral infections. In addition, the serum granulysin levels in patients with severe immunodeficiency treated bycell therapy fluctuated proportionately to the improvement of other immunological parameters. Our results suggest that granulysin is well associated with diverse activities of NK cells and CTL in physiological and pathological settings and could be a useful novel serum marker to evaluate the overall status of host cellular immunity.
Granulysin, a molecule expressed by human natural killer cells and activated T lymphocytes, exhibits cytolytic activity against a variety of microbes and tumors. Progress in understanding the structure, function and clinical relevance of granulysin over the past year encompasses three main areas: first, the solution of its crystal structure, providing new insights into its potential mechanism of target cell damage; second, inhibition of its function with small interfering RNA, indicating its relevance in microbial immunity; and third, association of granulysin expression in natural killer cells with good outcomes in cancer, indicating its potential utility as a diagnostic and suggesting its relevance to human disease.
Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice
- D Kagi
- B Ledermann
- K Burki
- P Seiler
- B Odermatt
- K J Olsen
- E R Podack
- R M Zinkernagel
- H Hengartner