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Individuals with increased inflammatory response to ozone demonstrate muted signaling of immune cell trafficking pathways
Fry, R., J. Rager, H. Zhou, B. Zou, J. Brickey, J. Ting, J. Lay, D. Peden, AND N. Alexis. Individuals with increased inflammatory response to ozone demonstrate muted signaling of immune cell trafficking pathways. Respiratory Research in operated by BioMed Central Limited. BioMed Central Ltd, London, Uk, 13(1):89, (2012).
Background Exposure to ozone activates innate immune function and causes neutrophilic (PMN) airway inflammation that in some individuals is robustly elevated. The interplay between immunoinflammatory function and genomic signaling in those with heightened inflammatory responsiveness to ozone is not well understood. Objectives Determine baseline predictors and post exposure discriminators for the immunoinflammatory response to ozone in inflammatory responsive adult volunteers. Methods Sputum induction was performed on 27 individuals before and after a two hour chamber exposure to 0.4 ppm ozone. Subjects were classified as inflammatory responders or nonresponders to ozone based on their PMN response. Innate immune function, inflammatory cell and cytokine modulation and transcriptional signaling pathways were measured in sputum. Results Post exposure. responders showed activated innate immune function (CDI6: 31,004 MFI vs 8988 MFI; CDI11b: 44,986 MFI vs 24,770 MFI; CD8O: 2236 MFI vs 1506 MFI: lL-8: 37,603 pg/nil vs 2828 pg/ml and IL-1B: 1380 pg/mI vs 318 pg/ml) with muted signaling of imniune cell trafficking pathways. In contrast, non-responders displayed decreased innate immune activity (CD16, CD80 phagocytosis: 2 particles/PMN vs 4 particles/PMN) post exposure that was accompanied by a heightened signaling of immune cell trafficking pathways. Conclusions Inflammatory responsive and non responsive individuals to ozone show an inverse relationship between immune cell trafficking amid immuno-inflammatory functional responses to ozone. These distinct genomic signatures may further our understanding about ozone-induced morbidity in individuals with different levels of inflammatory responsiveness.
In this study, our goal was to characterize factors in the airways that may contribute to the differential response of adult volunteers to ozone. Various cellular features associated with ozone responsiveness in the airways were assessed including the inflammatory response, innate immune function and transcriptional signaling both before and after ozone exposure.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION