Ozone-induced pulmonary inflammation and epithelial proliferation are partially mediated by PAF

Ozone (O-3) exposure stimulates airway inflammation and epithelial sloughin g in a number of species, including mice. Platelet-activating factor (PAF) is a lipid mediator released by activated mast cells, macrophages, and epit helial cells and causes pulmonary inflammation and hyperpermeability. We hy pothesized that the activation of PAF receptors is central to the developme nt of inflammation and epithelial injury induced by acute O-3 exposure in m ice. To test this hypothesis, O-3-susceptible C57BL/6J mice were treated wi th a PAF-receptor antagonist, UK-74505, or vehicle either before or immedia tely after 3-h exposure to O-3 (2 parts/million) or filtered air. Bronchoal veolar lavage (BAL) fluids were collected 6 and 24 h after exposure. Differ ential cell counts and protein content of the lavage were used as indicator s of inflammation in the airways. O-3-induced epithelial injury was assesse d by light microscopy, and DNA synthesis in epithelium of terminal bronchio les was estimated by using a bromodeoxyuridine-labeling index. Intercellula r adhesion molecule 1 (ICAM-1) expression was also examined in the lung by immunohistochemical localization. O-3 caused significant increases in polym orphonuclear leukocytes and protein in the BAL fluid, increased pulmonary e pithelial proliferation, and increased epithelial expression of ICAM-1 comp ared with air-exposed, vehicle-treated control mice. Relative to O-3-expose d, vehicle-treated control mice, UK-74505 before exposure significantly (P < 0.05) decreased BAL protein, polymorphonuclear leukocytes, and epithelial cells. O-3-induced inflammation was similarly attenuated in mice treated w ith UK-74505 after exposure. These experiments thus support the hypothesis that O-3-induced airways inflammation and epithelial damage in mice are par tially mediated by activation of PAF receptors, possibly through modulation of ICAM-1 expression.