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

Am J Respir Cell Mol Biol. 1994 Dec;11(6):707-15. doi: 10.1165/ajrcmb.11.6.7524571.


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.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / metabolism
  • Animals
  • Aorta / physiology
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Asbestos, Crocidolite / pharmacology*
  • Asbestos, Crocidolite / toxicity
  • Asbestos, Serpentine / pharmacology*
  • Asbestos, Serpentine / toxicity
  • Biological Assay
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Interferon-gamma / pharmacology*
  • Iron Carbonyl Compounds
  • L-Lactate Dehydrogenase / metabolism
  • Macrophages, Alveolar / metabolism*
  • Male
  • Muscle, Smooth, Vascular / physiology
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase
  • Organometallic Compounds / pharmacology
  • Organometallic Compounds / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Superoxide Dismutase / pharmacology
  • Up-Regulation / drug effects*
  • omega-N-Methylarginine


  • Asbestos, Serpentine
  • Culture Media, Conditioned
  • Organometallic Compounds
  • Asbestos, Crocidolite
  • Iron Carbonyl Compounds
  • omega-N-Methylarginine
  • Nitric Oxide
  • Interferon-gamma
  • Arginine
  • L-Lactate Dehydrogenase
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Amino Acid Oxidoreductases