HO-1 Regulates Inflammation at the Bite Site by Modulating Tissue Infiltration by Neutrophils and Inflammatory Monocytes (A-H) Mice ears exposed to 20 L. major-infected P. duboscqi sand flies. (A-E) Inflammatory infiltrate in mice ears. (A) Percentage of neutrophils, inflammatory monocytes (inflam. mo.), and resident myeloid cells (res. myeloid cells) (top panel); CD11b + IL-1B + cells (middle panel); Ly6G and Ly6C expression on CD11b + IL-1B + cells (bottom panel). (B) Number of CD11b + cells, inflammatory monocytes, neutrophils, and IL-1B + neutrophils. n = 4-6 pooled mice ears for (A) and (B). (C-E) Transmission to SnPPIX-treated or PBS-injected mice. Number of neutrophils (C) and inflammatory monocytes (D) in mice ears and mean fluorescent intensity (MFI) of CD11b on neutrophils (E) are shown. n = 4-6 pooled ears per replicate with 1-4 replicates/experiment. (F-H) Transmission to mice ears injected i.d. with CORM-2 or PBS. (F) Experimental design. (G) Total neutrophil number. (H) Number of IL-1B + neutrophils. n = 4-6 pooled mice ears. Representative plots (A) or cumulative data (B) of 2 experiments. Graphs represent mean ± SEM. Representative data from 3 (C and D) or 2 (E) experiments are shown. Cumulative data (G and H) from 5 experiments are shown. *p % 0.05; Mann-Whitney U-test (C-E, G, and H). See also Figures S2 and S4.

Contexts in source publication

Context 1

... next verified the nature of the inflammatory response after L. major-infected P. duboscqi sand flies. Similar to and 4B). Moreover, neutrophils accounted for 70% of the IL-1B + cells infiltrating the tissue at 6 h after sand fly bites ( Figures 4A and 4B). ...

Context 2

... to and 4B). Moreover, neutrophils accounted for 70% of the IL-1B + cells infiltrating the tissue at 6 h after sand fly bites ( Figures 4A and 4B). Coincidental to the induction of HO-1, IL-1B production decreased sharply by 24-48 h, despite a progressive infiltration of leukocytes. ...

Context 3

... to the induction of HO-1, IL-1B production decreased sharply by 24-48 h, despite a progressive infiltration of leukocytes. Accordingly, compared to controls, HO-1 inhibition by SnPPIX treatment significantly increased the infiltration of neutrophils and monocytes at 24 h after infected sand fly bites ( Figures 4C and 4D). Additionally, pharmacological inhibition of HO-1 in vivo also increased the mean fluorescence intensity of CD11b on neutrophils compared to PBS-injected animals, 24 h after infected bites ( Figure 4E), suggestive of their higher state of activation ( Keeney et al., 1993 (Fig- ure S4). ...

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... compared to controls, HO-1 inhibition by SnPPIX treatment significantly increased the infiltration of neutrophils and monocytes at 24 h after infected sand fly bites ( Figures 4C and 4D). Additionally, pharmacological inhibition of HO-1 in vivo also increased the mean fluorescence intensity of CD11b on neutrophils compared to PBS-injected animals, 24 h after infected bites ( Figure 4E), suggestive of their higher state of activation ( Keeney et al., 1993 (Fig- ure S4). However, the effect was not pronounced particularly for neutrophils ( Figure S4C), potentially due to the overall neutrophilia reported for HMOX1 R26D/D mice ( Devey et al., 2009). ...

Context 5

... compared to controls, HO-1 inhibition by SnPPIX treatment significantly increased the infiltration of neutrophils and monocytes at 24 h after infected sand fly bites ( Figures 4C and 4D). Additionally, pharmacological inhibition of HO-1 in vivo also increased the mean fluorescence intensity of CD11b on neutrophils compared to PBS-injected animals, 24 h after infected bites ( Figure 4E), suggestive of their higher state of activation ( Keeney et al., 1993 (Fig- ure S4). However, the effect was not pronounced particularly for neutrophils ( Figure S4C), potentially due to the overall neutrophilia reported for HMOX1 R26D/D mice ( Devey et al., 2009). ...

Context 6

... pharmacological inhibition of HO-1 in vivo also increased the mean fluorescence intensity of CD11b on neutrophils compared to PBS-injected animals, 24 h after infected bites ( Figure 4E), suggestive of their higher state of activation ( Keeney et al., 1993 (Fig- ure S4). However, the effect was not pronounced particularly for neutrophils ( Figure S4C), potentially due to the overall neutrophilia reported for HMOX1 R26D/D mice ( Devey et al., 2009). ...

Context 7

... test whether HO-1 exerts its anti-inflammatory effect through CO, we injected CO releasing molecule 2 (CORM-2) intradermally into mice ears. Administration of CORM-2 2 h after vector transmission ( Figure 4F) did not reduce the number of neutrophils infiltrating the ear ( Figure 4G) but resulted in a 60% decrease in the relative number of neutrophils secreting IL-1B ( Figure 4H). Collectively, these data provide evidence that the production of HO-1 in the skin dampens the acute inflammatory response induced by infected sand fly bites through the anti-inflammatory properties of its end products, including CO. ...

Context 8

... test whether HO-1 exerts its anti-inflammatory effect through CO, we injected CO releasing molecule 2 (CORM-2) intradermally into mice ears. Administration of CORM-2 2 h after vector transmission ( Figure 4F) did not reduce the number of neutrophils infiltrating the ear ( Figure 4G) but resulted in a 60% decrease in the relative number of neutrophils secreting IL-1B ( Figure 4H). Collectively, these data provide evidence that the production of HO-1 in the skin dampens the acute inflammatory response induced by infected sand fly bites through the anti-inflammatory properties of its end products, including CO. ...

Context 9

... test whether HO-1 exerts its anti-inflammatory effect through CO, we injected CO releasing molecule 2 (CORM-2) intradermally into mice ears. Administration of CORM-2 2 h after vector transmission ( Figure 4F) did not reduce the number of neutrophils infiltrating the ear ( Figure 4G) but resulted in a 60% decrease in the relative number of neutrophils secreting IL-1B ( Figure 4H). Collectively, these data provide evidence that the production of HO-1 in the skin dampens the acute inflammatory response induced by infected sand fly bites through the anti-inflammatory properties of its end products, including CO. ...