Fig 4
Incorporation of deuterated myristic acid and its elongation products into free fatty acids and triglycerides of lung tissue and blood plasma. Rats were fed 4.92 mol/g body wt d3-C14:0 and its presence and those of its elongation products palmitic (d3-C16:0) and stearic (d3-C18:0) acid determined in the free fatty acid (A, B) and triglyceride (C, D) fractions of lung tissue (A, C) and blood plasma (B, D) Deuterated fatty acids were determined after methylation by GC-MS as described in MATERIALS AND METHODS. Data are expressed as means SE of 4 experiments per data point. A, D: **P 0.01, ***P 0.001 vs. d3-C16:0 and d3-C18:0 of the corresponding time points; B, D: ‡ ‡P 0.01, ‡ ‡ ‡P 0.001 vs. 24 h of the respective fatty acid (d3-C14:0, d3-C16:0).
Source publication
Lung surfactant mainly comprises phosphatidylcholines (PC), together with phosphatidylglycerols and surfactant proteins SP-A to SP-D. Dipalmitoyl-PC (PC16:0/16:0), palmitoylmyristoyl-PC (PC16:0/14:0), and palmitoylpalmitoleoyl-PC (PC16:0/16:1) together comprise 75-80% of surfactant PC. During alveolarization, which occurs postnatally in the rat, PC...
Contexts in source publication
Context 1
... PC peaked at 24 h and then rapidly decreased in contrast to BALF and lung tissue PC (Fig. 3, C and D). Regarding the fatty acid substrates for lung PC synthesis, d 3 -C14:0 surmounted d 3 -C16:0 in both lung and plasma free fatty acids and triglycerides, while d 3 -C18:0 was below the detection level during the 48-h period of investiga- tion (Fig. 4, A-D). Again, for lung free fatty acids and triglyc- eride d 3 -C14:0 and d 3 -C16:0, concentrations were maintained for at least 48 h (Fig. 4, A and C), while in plasma, their concentrations peaked at 24 h and were nearly absent at 48 h (Fig. 4, B and ...
Context 2
... for lung PC synthesis, d 3 -C14:0 surmounted d 3 -C16:0 in both lung and plasma free fatty acids and triglycerides, while d 3 -C18:0 was below the detection level during the 48-h period of investiga- tion (Fig. 4, A-D). Again, for lung free fatty acids and triglyc- eride d 3 -C14:0 and d 3 -C16:0, concentrations were maintained for at least 48 h (Fig. 4, A and C), while in plasma, their concentrations peaked at 24 h and were nearly absent at 48 h (Fig. 4, B and ...
Context 3
... while d 3 -C18:0 was below the detection level during the 48-h period of investiga- tion (Fig. 4, A-D). Again, for lung free fatty acids and triglyc- eride d 3 -C14:0 and d 3 -C16:0, concentrations were maintained for at least 48 h (Fig. 4, A and C), while in plasma, their concentrations peaked at 24 h and were nearly absent at 48 h (Fig. 4, B and ...
Context 4
... d 3 -C12:0 values were much higher than those of d 3 -C14:0 and d 3 -C16:0. d 3 - C12:0 in lung triglycerides peaked at 24 h and then decreased, while its elongation products further increased (Fig. 5D) in contrast to exogenous d 3 -C14:0 experiments, where the d 3 - C14:0 concentration was maintained for 48 h in lung tissue triglycerides (Fig. ...
Citations
... GF and BI04 mice have similar low respiratory rates, whereas Cecum and reference SPF mice have similar and higher respiratory rates equivalent to what we have seen in other mouse studies (Sørli et al., 2018). The qualitative and quantitative compositions of lung surfactant are known to vary between species and according to conditions like temperature, breathing pattern, alveolar size, diet developmental stage or hibernation (Lang et al., 2005;Bernhard et al., 2007;Pynn et al., 2010;Suri et al., 2012). ...
Early-life changes to lung and gut microbiota have been linked to alterations in immune responses that may lead to pulmonary diseases later in life. Associations between early-life microbiota, germ-free status, lung gene expression, lung development and function are not well described. In this study, we compare early-life lung gene transcription under germ-free and different perinatal microbial exposures, and analyze with a predetermined focus on lung capacity and lung surfactant. We also analyze the later-in-life physiological measures of breathing patterns and lung surfactant function between the germ-free, gnotophoric and gnotobiotic offspring. To achieve this, we kept pregnant BALB/c germ-free mice in separate germ-free isolators until exposure to either A: no exposure (GF), B: Bifidobacterium animalis ssp. Lactis (BI04) or C: full cecum content harvested from other female SPF mice (Cecum). Subsequently, perinatally exposed offspring were used for the analyses. Lung tissue transcriptomics analysis was done at postnatal day 10 (PNday10) at the first phase of lung alveolar development. Head-out plethysmography for breathing pattern analysis was performed on the siblings at PNday23 followed by lung surfactant collection. The function of the collected lung surfactant was then analyzed ex vivo using the constrained drop surfactometer. Our results show that lung transcriptomics had differentially expressed genes related to surfactant turnover between groups and sex at PNday10. They also show that the GF and BI04 animals had lower respiratory rate than Cecum mice, or compared to age-matched specific pathogen-free (SPF) reference animals. We also see changes in lung surfactant function ex vivo. The overall conclusions are that 10-day-old GF mice do not have a markedly different lung gene transcription compared to gnotophoric or gnotobiotic mice, but genes related to surfactant metabolism are among the few differentially expressed genes. We show here for the first time that early-life microbiome status correlates with early-life surfactant-gene transcription and to later-in-life lung surfactant function and associated respiratory-rate changes in mice.
... Among the altered lipids, 8 were commonly reduced in lung and BALF, while none was commonly increased (Fig. 1B). [19,20] and another myristic acid containing PC (DMPC, 14:0-14:0) was one of the most reduced lipids in obese BALF, we performed targeted lipidomic studies using the standard compounds. We confirmed that DMPC and PMPC, but not the most abundant DPPC, were reduced in BALF of diet-induced obese mice (Fig. 1C-1E). ...
... In both HEK293T-ACE2 and Vero E6 cells, the addition of DMPC and PMPC to BALF from obese mice reversed the increased SARS-CoV-2 infection ( Fig. 2A-2B). In the second approach, we treated the HFD-fed obese mice with trimyristin, triglycerides of C14:0 myristic acid, and a precursor for BALF DMPC and PMPC [20]. Two weeks of trimyristin treatment did not alter body weight or glucose levels ( Fig. 2C-2D). ...
Objective
Obesity is an established risk factor for higher SARS-CoV-2 viral loads, severe COVID-19 pneumonia requiring hospitalization, and worse outcomes. However, the underlying mechanisms for the increased risk are not well understood. SARS-CoV-2 is a respiratory virus with the primary route of entry through the lungs, where the Spike protein of SARS-CoV-2 binds to the ACE2 receptor on pneumocytes. Lung surfactant produced by type II pneumocytes plays a major role in respiratory defense against infections. Surfactant predominantly contains lipids, especially phosphatidylcholines (PC), and obesity is characterized by aberrant lipid metabolism. We hypothesized that altered lipid composition in lung surfactant in obesity may promote SARS-CoV-2 infection, leading to severe COVID-19 disease.
Methods
Lipidomic analysis of lung tissue and bronchoalveolar lavage fluid (BALF) was performed using LC-MS/MS. The effects of PCs on SARS-CoV-2 pseudovirus infection were studied in HEK293T cells with ACE2 overexpression and in Vero-E6 cells with endogenous ACE2 expression. For the cell-cell fusion assay, HEK293T-ACE2 and HEK293T expressing SARS-CoV-2 Spike/eGFP were used as the target and effector cells, respectively.
Results
Lipidomic analysis revealed that myristic acid-containing dimyristoyl-PC (DMPC) and palmitoylmirystoyl-PC (PMPC) were reduced in lung tissue and BALF from high fat diet-induced obese mice. DMPC and PMPC markedly inhibited wild type and D614G mutant SARS-CoV-2 infection in HEK293T-ACE2 and Vero-E6 cells. Feeding obese mice with trimyristin, the triglycerides of myristic acid, increased DMPC and PMPC levels in lung surfactant. Lipid extract from BALF of trimyristin-treated obese mice mitigated the elevated wild type and D614G mutant SARS-CoV-2 infection. The inhibitory effects of DMPC and PMPC on SARS-CoV-2 infection were reversed by cholesterol.
Conclusions
The reduced DMPC and PMPC in lung surfactant may promote SARS-CoV-2 infection. Increasing DMPC and PMPC in lung surfactant could be an innovative strategy for preventing and treating severe COVID-19 disease in obesity.
... It has been recently demonstrated that the highly dehydrated state reached during the assembly of LBs, allows freshly secreted unused surfactant to maintain a ordered state up to temperatures well above 41 C [52], which could be important for a good surfactant to sustain breathing even under challenging physiological situations such as feverish episodes. Apart from DPPC, other minor amounts of disaturated phospholipid species complement surfactant and possibly modulate their behavior under slightly different contexts [53,54], according to adaptive processes that still need to be elucidated. ...
The lives of thousands premature babies have been saved along the last thirty years thanks to the establishment and consolidation of pulmonary surfactant replacement therapies (SRT). It took some time to close the gap between the identification of the biophysical and molecular causes of the high mortality associated with respiratory distress syndrome in very premature babies and the development of a proper therapy. Closing the gap required the elucidation of some key questions defining the structure-function relationships in surfactant as well as the particular role of the different molecular components assembled into the surfactant system. On the other hand, the application of SRT as part of treatments targeting other devastating respiratory pathologies, in babies and adults, is depending on further extensive research still required before enough amounts of good humanized clinical surfactants will be available. This review summarizes our current concepts on the compositional and structural determinants defining pulmonary surfactant activity, the principles behind the development of efficient natural animal-derived or recombinant or synthetic therapeutic surfactants, as well as a the most promising lines of research that are already opening new perspectives in the application of tailored surfactant therapies to treat important yet unresolved respiratory pathologies.
... Neutral lipids were separated from phospholipids using the chloroform phase of Bligh & Dyer extracts and disposable 100-mg NH2-propyl cartridges (Strata ® , Phenomenex, Aschaffenburg, Germany) as described before. Fatty acids were determined as fatty acid methyl esters (FAME) after transmethylation using docosatrienoic acid (C22:3n−3) as previously described [33], and 1 µL injected into a HP5890 gas chromatograph (GC) (Hewlett Packard) equipped with a flame ionization detector (250 °C), hydrogen/synthetic air as combustion gases, and a 100 m × 0.25 mm × 0.20 µm HP-88 column (Agilent, Germany) with helium as carrier gas. Column settings were 130 °C for 3 min, and then linearly increased to 176 °C at 27 min, 186 °C at 37 min, 190 °C at 58 min and 220 °C at 92 min. ...
Background
Arachidonic (ARA) and docosahexaenoic acid (DHA) are constitutive to membrane phospholipids, and essential for brain and overall development. ARA/DHA pools in term infants (TI) are built during the third trimester, stored as adipose tissue triglycerides and predominantly distributed via plasma phosphatidylcholine (PC). In preterm infants (PTI), placental ARA/DHA supply is replaced by linoleic-acid (LA)-enriched nutrition. This study aimed to investigate the impact of PTI nutrition, compared to placental supply, on fatty acid composition in adipose tissue and blood.Methods
Prospective observational study (4/2017–3/2019) in 12 PTI and 3 PTI with enterostomy (PTI/E) (gestational age (GA) < 32 weeks) with surgical intervention at term (± 6 weeks) and 14 TI (GA ≥ 34 weeks, surgical intervention < 2 weeks postnatally). PTI/E were analyzed descriptively only. PC and triglyceride fatty acids were analyzed with tandem mass spectrometry and gas chromatography, respectively. Results were compared between TI and PTI with Wilcoxon Test and shown as median [25th percentile–75th percentile] mol%.ResultsPTI had less ARA in adipose tissue TG (0.77[0.67–0.87]% vs. 1.04[0.95–1.14]%, p = 0.0003) and plasma PC (20.7[18.7–22.8]% vs. 28.3[22.7–33.5]%, p = 0.011) than TI. PTI also had less DHA in adipose tissue TG (0.6[0.4–0.8]% vs. 1.1[0.8–1.4]%, p = 0.006) and plasma PC (6.4[5.6–7.1]% vs. 8.4[7.8–13.1]%, p = 0.002). LA was increased in PTI’s adipose tissue TG (10.0[8.8–12.3]% vs. 3.0[2.5–3.6]%, p < 0.0001) and plasma PC (48.4[44.6–49.6]% vs. 30.6[24.9–35.6]%, p = 0.0002). Similar differences were observed in erythrocyte PC.Conclusion
In PTI, LA is increased and ARA/DHA decreased in adipose tissue, plasma and erythrocyte lipids as proxies for other tissues, likely caused by PTI nutrition. This may contribute to impaired PTI development.
... For this 100 µL organic phase was diluted with 2 mL toluolmethanol (4:1; v/v) comprising 10 µg/mL Z13, Z16, Z19, docosatetraenoic acid as an internal standard and 200 µL acetyl chloride for transesterification and subsequently transesterified as described before. 13,16,19-docosatrienoic (C22:3) was used as an internal standard [34,35]. ...
... This allowed for the separation of the fatty acids indicated in the results. Quantification was performed using calibration curves for the respective fatty acid methyl esters [34,35]. ...
... When initial choline concentration was high as exemplarily shown inFig. 3a, this was followed by a steep decrease within 28 days by 37(33)(34)(35)(36)(37)(38) %, whereas in individuals with low initial values this decrease amounted only 12 (4-27) %(Fig. 3b), although this difference was not significant (p > 0.05). ...
Background
Choline, docosahexaenoic acid (DHA), and arachidonic acid (ARA) are essential to fetal development, particularly of the brain. These components are actively enriched in the fetus. Deprivation from placental supply may therefore result in impaired accretion in preterm infants. Objective
To determine choline, choline metabolites, DHA, and ARA in human breast milk (BM) of preterm infants compared to BM of term born infants. DesignWe collected expressed BM samples from 34 mothers (N = 353; postnatal day 6–85), who had delivered 35 preterm infants undergoing neonatal intensive care (postmenstrual age 30 weeks, range 25.4–32.0), and from mothers after term delivery (N = 9; postnatal day 6–118). Target metabolites were analyzed using tandem mass spectrometry and gas chromatography and reported as medians and 25th/75th percentiles. ResultsIn BM, choline was mainly present in the form of phosphocholine and glycerophosphocholine, followed by free choline, phosphatidylcholine, sphingomyelin, and lyso-phosphatidylcholine. In preterm infants’ BM total choline ranged from 61 to 360 mg/L (median: 158 mg/L) and was decreased compared to term infants’ BM (range 142–343 mg/L; median: 258 mg/L; p < 0.01). ARA and DHA comprised 0.81 (range: 0.46–1.60) and 0.43 (0.15–2.42) % of total preterm BM lipids, whereas term BM values were 0.68 (0.52–0.88) and 0.35 (0.18–0.75) %, respectively. Concentrations of all target parameters decreased after birth, and frequently 150 ml/kg/d BM did not meet the estimated fetal accretion rates. Conclusions
Following preterm delivery, BM choline concentrations are lower, whereas ARA and DHA levels are comparable versus term delivery. Based on these findings we suggest a combined supplementation of preterm infants’ BM with choline, ARA and DHA combined to improve the nutritional status of preterm infants. Study registrationThis study was registered at www.clinicaltrials.gov. Identifier: NCT01773902.
... It is worth noting, however, that mixtures based on monounsaturated PC species can generate very low surface tension values under appropriate conditions of surface film compression (Crane and Hall, 2001) and that DPPC is not universally the major component of surfactant. For instance, DPPC is largely replaced by the monounsaturated PC species palmitoylpalmitoleoyl PC (PC16:0/16:1) in a number of fast breathing and in some heterothermic mammals (Lang et al., 2005) and by the shorter chain saturated species palmitoylmyristoyl PC (PC16:0/14:0) in sucking rats, due the high content of myristic acid in rat milk (Pynn et al., 2010). Moreover, this diversity of surfactant lipid composition is equally applicable to human development. ...
The pathways and mechanisms that regulate pulmonary surfactant synthesis, processing, secretion and catabolism have been extensively characterised using classical biochemical and analytical approaches. These have constructed a model, largely in experimental animals, for surfactant phospholipid metabolism in the alveolar epithelial cell whereby phospholipid synthesised on the endoplasmic reticulum is selectively transported to lamellar body storage vesicles, where it is subsequently processed before secretion into the alveolus. Surfactant phospholipid is a complex mixture of individual molecular species defined by the combination of esterified fatty acid groups and a comprehensive description of surfactant phospholipid metabolism requires consideration of the interactions between such molecular species. However, until recently, lipid analytical techniques have not kept pace with the considerable advances in understanding of the enzymology and molecular biology of surfactant metabolism. Refinements in electrospray ionisation mass spectrometry (ESI-MS) can now provide very sensitive platforms for the rapid characterisation of surfactant phospholipid composition in molecular detail. The combination of ESI-MS and administration of phospholipid substrates labelled with stable isotopes extends this analytical approach to the quantification of synthesis and turnover of individual molecular species of surfactant phospholipid. As this methodology does not involve radioactivity, it is ideally suited to application in clinical studies. This review will provide an overview of the metabolic processes that regulate the molecular specificity of surfactant phosphatidylcholine together with examples of how the application of stable isotope technologies in vivo has, for the first time, begun to explore regulation of the molecular specificity of surfactant synthesis in human subjects.
... Whether this will affect long-term outcome of patients, is not clear. However, there is experimental evidence that molecular adaptation of surfactant to lung physiology and development may affect alveolar homeostasis Pynn et al., 2010;Gille et al., 2007). In this short review, the functional background of lung surfactant, its molecular diversity and the implementation of pulmonary surfactant metabolism into an integrative concept of pulmonary and systemic phospholipid metabolism will be addressed. ...
Lung surfactant is a complex with a unique phospholipid and protein composition. Its specific function is to reduce surface tension at the pulmonary air–liquid interface. The underlying Young–Laplace equation, applying to the surface of any geometrical structure, is the more important the smaller its radii are. It therefore applies to the alveoli and bronchioli of mature lungs, as well as to the tubules and saccules of immature lungs. Surfactant comprises 80% phosphatidylcholine (PC), of which dipalmitoyl-PC, palmitoyl-myristoyl-PC and palmitoyl-palmitoleoyl-PC together are 75%. Anionic phosphatidylglycerol and cholesterol are about 10% each, whereas surfactant proteins SP-A to -D comprise 2–5%. Maturation of the surfactant system is not essentially due to increased synthesis but to decreased turnover of specific components. Molecular differences correlate with resting respiratory rate (RR), where PC16:0/16:0 is the lower the higher RR is. PC16:0/14:0 is increased during alveolar formation, and decreases immune reactions that might impair alveolar development. In rigid bird lungs, with air-capillaries rather than alveoli, and no surface area changes during the respiratory cycle, PC16:0/16:0 is highest and PC16:0/14:0 absent. As there is no need for a surface-associated surfactant reservoir, SP-C is absent in birds as well. Airflow is lowest and particle sedimentation highest in the extrapulmonary air-sacs, rather than in the gas-exchange area. Consequently, SP-A and -D for particle opsonization are absent in bird surfactant. In essence, comparative analysis is consistent with the concept that surfactant is adapted to the physiologic needs of a given vertebrate species at a given developmental stage.
... Our data show that the composition of PC molecular species in LLF was not substantially altered by any treatment (see RESULTS, Fig. 1A). This is in line with previous findings that it mostly depends on metabolic and nutritional factors (35). In lung tissue, however, rhuKGF, betamethasone, and their combination increased the fraction of components enriched in surfactant (surf-PC). ...
Background:
Surfactant, synthesized by type II pneumocytes (PN-II), mainly comprises phosphatidylcholine (PC) and is essential to prevent neonatal respiratory distress. Furthermore, PC is essential to lung tissue growth and maintenance as a membrane component. Recent findings suggest the lung contributes to systemic lipid homeostasis via PC export through ABC-A1 transporter expression. Hence, it is important to consider pharmacological interventions in neonatal lung PC metabolism with respect to such export.
Methods:
5d old rats were treated with carrier (control), betamethasone (intraperitoneally), recombinant human keratinocyte growth factor (rhuKGF) (subcutaneously) or their combination for 48h. Animals were intraperitoneally injected with 50mg/kg [D9-methyl]choline chloride 1.5, 3.0 and 6.0h prior to sacrifice at d7, and lung lavage fluid (LLF) and tissue harvested. Endogenous PC, D9-labeled PC species and their water-soluble precursors (D9-)choline and (D9-)phosphocholine were determined by tandem mass spectrometry.
Results:
Treatment increased secreted and tissue PC pools, but did not change equilibrium composition of PC species in LLF. However, all treatments increased specific surfactant components in tissue. In controls, peak D9-PC in lavaged lung was reached after 3h, and was decreased at 6h. Only 13% of this net loss in lavaged lung was found in LLF. Such decrease was also present in lungs treated with betamethasone, but not with rhuKGF alone. D9-PC loss at 3-6h and PC synthesis calculated from D9-enrichment of phosphocholine indicated that daily synthesis rate is higher than total pool size.
Conclusion:
Lung tissue contributes to systemic PC homeostasis in neonatal rats, which is altered by glucocorticoid and rhuKGF treatment.
... Samples were extracted according to Bligh and Dyer [25], and the respective hydrophilic upper phase containing the water soluble precursors or metabolitesand organic lower phase containing the lipids were then subjected for further analyses. Total phospholipids in the organic phase were determined according to Bartlett after digestion of the organic compounds as previously described [26]. Comparison of EDTA plasma and serum for total phospholipid, PC and PC molecular species analysis with HPLC (see below) showed no differences in these parameters (data not shown). ...
... Patients were mobile and were allowed to drink water during the infusion. Eating was allowed following completion of High performance liquid chromatography of plasma PC Routine analysis of PC molecular species and sphingomyelin (SPH) was performed from lipid extracts using high performance liquid chromatography (HPLC) as described before [26]. Briefly, PC/SPH was prepared from 500nmol plasma phospholipid aliquots using 100mg Strata NH 2 disposable cartridges (Phenomenex Inc., USA) and dimyristoyl-PC as an internal standard. ...
... To address characteristic differences of choline and PC metabolism and plasma kinetics we employed, for the first time in CF patients, in vivo labeling with [D 9 -methyl]choline [21,26]. This enabled us to investigate de novo synthesis of PC via direct [D 9 -methyl]choline incorporation, the major source of mono-and di-unsaturated PC in plasma, resulting in the formation of D 9 -labeled PC [21,26]. ...
Liver impairment, ranging from steatosis to cirrhosis, is frequent in cystic fibrosis (CF) patients and is becoming increasingly significant due to their improved life expectancy. One aspect of hepatic alterations is caused by increased fecal loss of the essential nutrient choline, following enterohepatic bile phosphatidylcholine (PC) cycle impairment. Hepatic PC synthesis, both de novo and via phosphatidylethanolamine-N-methyl-transferase (PEMT), is essential for very low-density lipoprotein (VLDL) secretion. VLDL-PC in particular contributes to the organism's supply with polyunsaturated fatty acids (LC-PUFA), namely arachidonic (C20:4) and docosahexaenoic acid (C22:6). Consequently, choline deprivation and altered hepatic PC metabolism may affect plasma PC homeostasis and extrahepatic organ function.
To investigate relationships between altered plasma choline and PC homeostasis and markers of lung function and inflammation in CF. To assess alterations in hepatic choline and PC metabolism of CF patients.
Quantification of plasma/serum choline and PC species in adult CF patients compared to controls. Correlation of PC with forced expiratory vital capacity (FEV1) and interleukin 6 (IL-6) concentrations. Analysis of choline and PC metabolism in CF compared to controls, using deuterated choline ([D9-methyl]-choline) labeling in vivo.
Mean choline and PC concentrations in CF patients were lower than in controls. Choline and PC concentrations as well as fractions of C22:6-PC and C20:4-PC correlated directly with FEV1, but inversely with IL-6. Plasma concentrations of deuterated PC were decreased for both pathways, whereas only in PC synthesized via PEMT precursor enrichment was decreased.
In CF patients, hepatic and plasma homeostasis of choline and PC correlate with lung function and inflammation. Impaired hepatic PC metabolism, exemplarily shown in three CF patients, provides an explanation for such correlations. Larger studies are required to understand the link between hepatic PC metabolism and overall clinical performance of CF patients, and the perspective of choline substitution of these patients. © 2015 S. Karger AG, Basel.
... It is envisioned that similar and new cases of these rare entities will be merged internationally, to increase the pool of specific diseases available for analysis. This will also make possible to investigate other confounding factors like age or diet [40]. ...
Lipids account for the majority of pulmonary surfactant, which is essential for normal breathing. We asked if interstitial lung diseases (ILD) in children may disrupt alveolar surfactant and give clues for disease categorization.
Comprehensive lipidomics profiles of broncho-alveolar lavage fluid were generated in 115 children by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Two reference populations were compared to a broad range of children with ILD.
Class and species composition in healthy children did not differ from that in children with ILD related to diffuse developmental disorders, chronic tachypnoe of infancy, ILD related to lung vessels and the heart, and ILD related to reactive lymphoid lesions. As groups, ILDs related to the alveolar surfactant region, ILD related to unclear respiratory distress syndrome in the mature neonate, or in part ILD related to growth abnormalities reflecting deficient alveolarisation, had significant alterations of some surfactant specific phospholipids. Additionally, lipids derived from inflammatory processes were identified and differentiated. In children with ABCA3-deficiency from two ILD causing mutations saturated and monounsaturated phosphatidylcholine species with 30 and 32 carbons and almost all phosphatidylglycerol species were severely reduced. In other alveolar disorders lipidomic profiles may be of less diagnostic value, but nevertheless may substantiate lack of significant involvement of mechanisms related to surfactant lipid metabolism.
Lipidomic profiling may identify specific forms of ILD in children with surfactant alterations and characterized the molecular species pattern likely to be transported by ABCA3 in vivo.
