Factors that influence the suppression of pulmonary antibacterial defenses in mice exposed to ozone.
Exposure to ozone (O3) has been shown to increase susceptibility of mice to bacterial infection; however, the underlying mechanism has not been well elucidated. This study investigated the effect of O3 exposure on the ability of mice to combat an infectious challenge of Streptococcus zooepidemicus. Following a 3-h exposure to either air, 0.4 ppm O3, or 0.8 ppm O3, 5- and 9-week-old mice received an aerosol infection of bacteria. Intrapulmonary killing of the bacteria was impaired in the O3-exposed mice. The effect was most severe at the higher dose of O3 in the younger mice, and showed good correlation to subsequent mortality assessed over a 20-day period. Alveolar macrophages (AM) from O3-exposed mice had an impaired ability to phagocytose the bacteria. Additionally, prostaglandin E2 (PGE2) levels, which are known to depress AM function, were increased in the bronchoalveolar lavage fluid of the younger mice following exposure to O3, while pretreatment with indomethacin in the drinking water blunted the increased of PGE2 and reduced O3 enhanced mortality from 53 to 33%. The data show that O3 inhalation can reduce the defensive capability of the murine lung and that this is associated with a reduction in AM phagocytosis. The defect is more marked in young mice, suggesting that they may be more susceptible to oxidant exposure. Further studies are required to distinguish between direct toxicity of O3 on the AM and indirect suppression due to modulation of pharmacologic or inflammatory mediators.
Gilmour
M I
MI
Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill.
Park
P
P
Doerfler
D
D
Selgrade
M K
MK
D000276:Adjuvants, Immunologic / Q000096:biosynthesis / Q000502:physiology; D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D007113:Immunity, Innate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008171:Lung Diseases / Q000139:chemically induced / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D010126:Ozone / Q000633:toxicity*; D010587:Phagocytosis / Q000187:drug effects; D013290:Streptococcal Infections / Q000139:chemically induced / Q000276:immunology*
D000276:Adjuvants, Immunologic; D010126:Ozone; D015232:Dinoprostone; D007213:Indomethacin