INHIBITION OF MACROPHAGES WITH GADOLINIUM CHLORIDE ABROGATES OZONE-INDUCED PULMONARY INJURY AND INFLAMMATORY MEDIATOR PRODUCTION

Acute inhalation of toxic doses of ozone (O-3) induces macrophage accu mulation in the lung and the release of cytotoxic and proinflammatory mediators. To evaluate the role of macrophages and their mediators in the pathophysiologic response of the lung to O-3, we examined the effe cts of the macrophage inhibitor, gadolinium chloride (GdCl3), on O-3-i nduced inflammation, mediator production, and lavage fluid protein lev els. Rats were pretreated with GdCl3 (7 mg/kg, intravenously) or contr ol 24 h prior to exposure to air or O-3 (2 parts per million, 3 h). An imals were killed 48 h after exposure. GdCl3 pretreatment of rats was found to abrogate O-3-induced increases in the number of cells, as wel l as the amount of protein recovered in bronchoalveolar lavage fluid. Following GdCl3 pretreatment of rats, lung lavage cells consisting of > 90% macrophages were found to produce significantly less nitric oxid e and express less inducible nitric oxide synthase (iNOS) when compare d to cells from rats exposed to O-3. O-3-induced alterations in supero xide anion production by alveolar macrophages, both in vitro and in si tu, were also attenuated by GdCl3 pretreatment of rats. In addition, i ncreases in tumor necrosis factor alpha (TNF-alpha) and fibronectin in lung tissue induced by O-3 were reduced. Taken together, these data p rovide support for the hypothesis that macrophages contribute to the p athogenesis of O-3-induced lung injury.