KJ Pendino, RL Shuler, JD Laskin and DL Laskin
Department of Pharmacology and Toxicology, Rutgers University, Piscataway, NJ 08855-0789.

Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and fibronectin are macrophage-derived mediators thought to be important in the pathogenesis of lung injury, inflammation, and fibrosis. In the present studies, we examined the effects of acute exposure of rats to the pulmonary irritant, ozone (O3), on production of these mediators by lung phagocytes. Cells were isolated from lungs 48 h after exposure of rats to air or O3 (2 ppm, 3 h). We found that cells from O3-exposed rats released 2- to 3-fold more IL-1 and TNF-alpha into the culture medium than did cells from air-exposed rats. These effects were time dependent, reaching a maximum at 2 and 24 h for IL-1, and 2 to 4 h for TNF-alpha. We also found that alveolar macrophages from O3-treated rats produced increased amounts of fibronectin, both alone and in response to transforming growth factor-beta, lipopolysaccharide, and interferon- gamma when compared with cells from control rats. Examination of immunohistochemically stained tissue sections indicated increased IL-1, TNF-alpha, and fibronectin in lungs from O3-exposed animals when compared with control animals. IL-1 and TNF-alpha were localized in lung macrophages, whereas fibronectin was associated with blood vessel walls and the lung interstitium. These results demonstrate that lung phagocyte production of these inflammatory mediators is elevated following O3 exposure and suggest that they may play a role in oxidant- induced pulmonary inflammation and injury.

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