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Title: Inhibition of macrophages with gadolinium chloride abrogates ozone-induced pulmonary injury and inflammatory mediator production.

Authors: Pendino, K J; Meidhof, T M; Heck, D E; Laskin, J D; Laskin, D L

Published In Am J Respir Cell Mol Biol, (1995 Aug)

Abstract: Acute inhalation of toxic doses of ozone (O3) induces macrophage accumulation 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 O3, we examined the effects of the macrophage inhibitor, gadolinium chloride (GdCl3), on O3-induced inflammation, mediator production, and lavage fluid protein levels. Rats were pretreated with GdCl3 (7 mg/kg, intravenously) or control 24 h prior to exposure to air or O3 (2 parts per million, 3 h). Animals were killed 48 h after exposure. GdCl3 pretreatment of rats was found to abrogate O3-induced increases in the number of cells, as well 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 oxide and express less inducible nitric oxide synthase (iNOS) when compared to cells from rats exposed to O3. O3-induced alterations in superoxide anion production by alveolar macrophages, both in vitro and in situ, were also attenuated by GdCl3 pretreatment of rats. In addition, increases in tumor necrosis factor alpha (TNF-alpha) and fibronectin in lung tissue induced by O3 were reduced. Taken together, these data provide support for the hypothesis that macrophages contribute to the pathogenesis of O3-induced lung injury.

PubMed ID: 7542894 Exiting the NIEHS site

MeSH Terms: Amino Acid Oxidoreductases; Animals; Anions/metabolism; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal/pharmacology*; Bronchoalveolar Lavage Fluid/chemistry; Bronchoalveolar Lavage Fluid/cytology; Cell Count; Drug Administration Schedule; Female; Fibronectins/metabolism; Gadolinium/pharmacology*; Immunohistochemistry; Inflammation Mediators/immunology*; Lung/immunology*; Macrophages, Alveolar/cytology; Macrophages, Alveolar/drug effects*; Nitric Oxide Synthase; Nitric Oxide/biosynthesis; Nitric Oxide/metabolism; Ozone; Rats; Rats, Sprague-Dawley; Superoxides/metabolism; Time Factors; Tumor Necrosis Factor-alpha/metabolism

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