Ambient ozone primes pulmonary innate immunity in mice.
Exposure to ozone in air pollution in urban environments is associated with increases in pulmonary-related hospitalizations and mortality. Because ozone also alters clearance of pulmonary bacterial pathogens, we hypothesized that inhalation of ozone modifies innate immunity in the lung. To address our hypothesis, we exposed C57BL/6J mice to either free air or ozone, and then subsequently challenged with an aerosol of Escherichia coli LPS. Pre-exposure to ozone resulted in [corrected] higher concentrations of both total protein and proinflammatory cytokines in lung lavage fluid, enhanced LPS-mediated signaling in lung tissue, and higher concentrations of serum IL-6 following inhalation of LPS. However, pre-exposure to ozone dramatically reduced inflammatory cell accumulation to the lower airways in response to inhaled LPS. The reduced concentration of cells in the lower airways was associated with enhanced apoptosis of both lung macrophages and systemic circulating monocytes. Moreover, both flow cytometry and confocal microscopy indicate that inhaled ozone causes altered distribution of TLR4 on alveolar macrophages and enhanced functional response to endotoxin by macrophages. These observations indicate that ozone exposure increases both the pulmonary and the systemic biologic response to inhaled LPS by priming the innate immune system.
Hollingsworth
John W
JW
Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University Medical Center, Box 3136, Durham, NC 27710, USA. holli017@mc.duke.edu
Maruoka
Shuichiro
S
Li
Zhuowei
Z
Potts
Erin N
EN
Brass
David M
DM
Garantziotis
Stavros
S
Fong
Alan
A
Foster
W Michael
WM
Schwartz
David A
DA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers; D048749:Cytokinesis / Q000187:drug effects; D004789:Enzyme Activation; D007113:Immunity, Innate / Q000187:drug effects* / Q000276:immunology*; D001239:Inhalation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010126:Ozone / Q000494:pharmacology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D015415:Biomarkers; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D010126:Ozone; D020928:Mitogen-Activated Protein Kinases