Am. J. Respir. Cell Mol. Biol., Vol 11, No. 6, 12 1994, 707-715.
Asbestos fibers and interferon-gamma up-regulate nitric oxide production in rat alveolar macrophages
G Thomas, T Ando, K Verma and E Kagan
Department of Pathology, Georgetown University School of Medicine, Washington, DC.
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.
