Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages

American Journal of Respiratory Cell and Molecular Biology
G ThomasE Kagan

Abstract

The present study was undertaken to determine whether asbestos exposure induces the formation of nitric oxide (NO.) radical by rat alveolar macrophages (AM). For this purpose, AM from Sprague-Dawley rats were cultured for 48 h in the presence or absence of either chrysotile (serpentine) or crocidolite (amphibole) asbestos fibers. The effects of asbestos fibers were compared with those of nonfibrogenic carbonyl iron particles. Nitrite (NO2-), the stable oxidation product of NO. in macrophage conditioned medium, was assayed by the Griess reaction. Production of NO2- by AM was significantly increased by both chrysotile (P < 0.01) and crocidolite (P < 0.05) asbestos fibers (10 micrograms/ml). Since interferon-gamma (IFN-gamma) is known to induce NO. synthase within macrophages, and since elevated levels of intrapulmonary IFN-gamma have been noted in asbestos workers, the combined effects of asbestos and IFN-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 had no significant effect on NO. production by AM. NO2- production was significantly attenuated by the NO. synthase inhibit...Continue Reading

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