title: Individuals with increased inflammatory response to ozone demonstrate muted signaling of immune cell trafficking pathways.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Fry
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rager
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhou
authors.forename: Baiming
authors.initials: B
authors.lastname: Zou
authors.forename: June W
authors.initials: JW
authors.lastname: Brickey
authors.forename: Jenny
authors.initials: J
authors.lastname: Ting
authors.forename: John C
authors.initials: JC
authors.lastname: Lay
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
authors.forename: Neil E
authors.initials: NE
authors.lastname: Alexis
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate / Q000187:drug effects*; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D010126:Ozone / Q000009:adverse effects*; D010587:Phagocytosis / Q000187:drug effects; D010641:Phenotype; D016897:Respiratory Burst / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013183:Sputum / Q000276:immunology; D049490:Systems Biology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D010126:Ozone