Asbestos-induced nitric oxide production: synergistic effect with interferon-gamma.
This study has shown, for the first time, that in vitro exposure of rat AMs to either crocidolite (amphibole) or chrysotile (serpentine) asbestos fibers induces the synthesis not only of the O2*- anion, but also of the nitrogen radical, NO*. Furthermore, this asbestos-related effect is enhanced in the presence of interferon-gamma. NO* has been implicated in several pathologic reactions, such as inflammation and immune complex-mediated cell injury. Additionally, NO* may interact with secondary amines to generate nitrosamines, which are potent carcinogens. Our findings could represent a novel type of asbestos-mediated injury, and we propose that the injurious effects of asbestos might be mediated via the interaction of NO* with O2*-, with the generation of ONOO- and other potent toxic free radicals.
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia 20007.
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017638:Asbestos, Crocidolite / Q000494:pharmacology*; D017632:Asbestos, Serpentine / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D007371:Interferon-gamma / Q000494:pharmacology*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D019323:omega-N-Methylarginine
D017632:Asbestos, Serpentine; D017638:Asbestos, Crocidolite; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D013482:Superoxide Dismutase