ASBESTOS FIBERS AND INTERFERON-GAMMA UP-REGULATE NITRIC-OXIDE PRODUCTION IN RAT ALVEOLAR MACROPHAGES

The present study was undertaken to determine whether asbestos exposur e induces the formation of nitric oxide (NO.) radical by rat alveolar macrophages (AM). For this purpose, AM from Sprague-Dawley rats were c ultured for 48 h in the presence or absence of either chrysotile (serp entine) or crocidolite (amphibole) asbestos fibers. The effects of asb estos fibers were compared with those of nonfibrogenic carbonyl iron p articles. Nitrite (NO2-), the stable oxidation product of NO. in macro phage conditioned medium, was assayed by the Griess reaction. Producti on of NO2- by AM was significantly increased by both chrysotile (P < 0 .01) and crocidolite (P < 0.05) asbestos fibers (10 mu g/ml). Since in terferon-gamma (IFN-gamma) is known to induce NO. synthase within macr ophages, and since elevated levels of intrapulmonary IFN-gamma have be en noted in asbestos workers, the combined effects of asbestos and lFN -gamma also were studied in the context of NO. formation. Addition of IFN-gamma (250 to 500 IU/ml) synergistically enhanced the formation of NO2- induced by chrysotile and crocidolite. Notably, carbonyl iron ha d no significant effect on NO. production by AM. NO; production was si gnificantly attenuated by the NO. synthase inhibitor, N-G-monomethyl-L -arginine (0.5 to 1 mg/ml). By contrast, superoxide dismutase (150 U/m l) significantly enhanced asbestos-induced NO2- production by AM (P < 0.001). Since superoxide anion can interact with NO. to generate the t oxic hydroxyl radical, and since superoxide dismutase is known to prot ect against asbestos-induced injury, the induction of NO. radical by a sbestos fibers may represent a novel form of asbestos-related injury.