title: Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages.
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 inhibitor, NG-monomethyl-L-arginine (0.5 to 1 mg/ml). By contrast, superoxide dismutase (150 U/ml) significantly enhanced asbestos-induced NO2- production by AM (P < 0.001). Since superoxide anion can interact with NO. to generate the toxic hydroxyl radical, and since superoxide dismutase is known to protect against asbestos-induced injury, the induction of NO. radical by asbestos fibers may represent a novel form of asbestos-related injury.
authors.affiliation: Department of Pathology, Georgetown University School of Medicine, Washington, DC.
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: T
authors.initials: T
authors.lastname: Ando
authors.forename: K
authors.initials: K
authors.lastname: Verma
authors.forename: E
authors.initials: E
authors.lastname: Kagan
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D017638:Asbestos, Crocidolite / Q000494:pharmacology* / Q000633:toxicity; D017632:Asbestos, Serpentine / Q000494:pharmacology* / Q000633:toxicity; D001681:Biological Assay; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D054354:Iron Carbonyl Compounds; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase; D009942:Organometallic Compounds / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D019323:omega-N-Methylarginine
chemical_list: D017632:Asbestos, Serpentine; D017077:Culture Media, Conditioned; D009942:Organometallic Compounds; D017638:Asbestos, Crocidolite; D054354:Iron Carbonyl Compounds; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D000594:Amino Acid Oxidoreductases