Abstract | BACKGROUND: Exposure to ozone activates innate immune function and causes neutrophilic (PMN) airway inflammation that in some individuals is robustly elevated. The interplay between immuno-inflammatory 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 immuno-inflammatory 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 non-responders 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 (CD16: 31,004 MFI vs 8988 MFI; CD11b: 44,986 MFI vs 24,770 MFI; CD80: 2236 MFI vs 1506 MFI; IL-8: 37,603 pg/ml vs 2828 pg/ml; and IL-1β: 1380 pg/ml vs 318 pg/ml) with muted signaling of immune 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 and 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.
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Authors | Rebecca C Fry, Julia E Rager, Haibo Zhou, Baiming Zou, June W Brickey, Jenny Ting, John C Lay, David B Peden, Neil E Alexis |
Journal | Respiratory research
(Respir Res)
Vol. 13
Pg. 89
(Oct 03 2012)
ISSN: 1465-993X [Electronic] England |
PMID | 23033980
(Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Air Pollutants
- Biomarkers
- Cytokines
- Inflammation Mediators
- Ozone
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Topics |
- Adult
- Air Pollutants
(adverse effects)
- Asthma
(chemically induced, genetics, immunology)
- Biomarkers
(metabolism)
- Cell Movement
(drug effects)
- Cytokines
(metabolism)
- Female
- Gene Expression Profiling
- Genetic Predisposition to Disease
- Humans
- Hypersensitivity, Immediate
(chemically induced, genetics, immunology)
- Immunity, Innate
(drug effects)
- Inflammation
(chemically induced, genetics, immunology)
- Inflammation Mediators
(metabolism)
- Inhalation Exposure
(adverse effects)
- Lung
(drug effects, immunology)
- Macrophages
(drug effects, immunology)
- Male
- Neutrophils
(drug effects, immunology)
- Ozone
(adverse effects)
- Phagocytosis
(drug effects)
- Phenotype
- Respiratory Burst
(drug effects)
- Signal Transduction
(drug effects)
- Sputum
(immunology)
- Systems Biology
- Time Factors
- Transcription, Genetic
(drug effects)
- Young Adult
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