Ozone (O3) exposure stimulates airway
inflammation and epithelial sloughing in a number of species, including mice.
Platelet-activating factor (PAF) is a
lipid mediator released by activated mast cells, macrophages, and epithelial cells and causes
pulmonary inflammation and hyperpermeability. We hypothesized that the activation of
PAF receptors is central to the development of
inflammation and epithelial injury induced by acute O3 exposure in mice. To test this hypothesis, O3-susceptible C57BL/6J mice were treated with a PAF-receptor antagonist,
UK-74505, or vehicle either before or immediately after 3-h exposure to O3 (2 parts/million) or filtered air. Bronchoalveolar lavage (BAL) fluids were collected 6 and 24 h after exposure. Differential cell counts and
protein content of the lavage were used as indicators of
inflammation in the airways. O3-induced epithelial injury was assessed by light microscopy, and
DNA synthesis in epithelium of terminal bronchioles was estimated by using a
bromodeoxyuridine-labeling index.
Intercellular adhesion molecule 1 (ICAM-1) expression was also examined in the lung by immunohistochemical localization. O3 caused significant increases in polymorphonuclear leukocytes and
protein in the BAL fluid, increased pulmonary epithelial proliferation, and increased epithelial expression of
ICAM-1 compared with air-exposed, vehicle-treated control mice. Relative to O3-exposed, vehicle-treated control mice,
UK-74505 before exposure significantly (P < 0.05) decreased BAL
protein, polymorphonuclear leukocytes, and epithelial cells. O3-induced
inflammation was similarly attenuated in mice treated with
UK-74505 after exposure. These experiments thus support the hypothesis that O3-induced airways
inflammation and epithelial damage in mice are partially mediated by activation of
PAF receptors, possibly through modulation of
ICAM-1 expression.