Individuals with increased inflammatory response to ozone demonstrate muted signaling of immune cell trafficking pathways Public Deposited

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Creator
  • Fry, Rebecca
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Zou, Baiming
    • Affiliation: Gillings School of Global Public Health, Department of Biostatistics
  • Peden, David
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Department of Pediatrics
  • Alexis, Neil
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Department of Pediatrics
  • Ting, Jenny P.-Y.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Zhou, Haibo
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Gillings School of Global Public Health, Department of Biostatistics
  • Rager, Julia E
    • Affiliation: Gillings School of Global Public Health, Department of Environmental Sciences and Engineering
  • Brickey, June W
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Lay, John C
    • Affiliation: School of Medicine, Center for Environmental Medicine, Asthma and Lung Biology, Department of Pediatrics
Abstract
  • 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.
Date of publication
Identifier
  • doi:10.1186/1465-9921-13-89
  • 23033980
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Rebecca C Fry et al.; licensee BioMed Central Ltd.
License
Journal title
  • Respiratory Research
Journal volume
  • 13
Journal issue
  • 1
Page start
  • 89
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1465-9921
Bibliographic citation
  • Respiratory Research. 2012 Oct 03;13(1):89
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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