Thomas G, Ando T, Verma K, Kagan E
Department of Pathology, Georgetown University School of Medicine, Washington, DC.
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.
本研究旨在确定接触石棉是否会诱导大鼠肺泡巨噬细胞（AM）形成一氧化氮（NO.）自由基。为此，将来自Sprague-Dawley大鼠的AM在存在或不存在温石棉（蛇纹石）或青石棉（闪石）石棉纤维的情况下培养48小时。将石棉纤维的作用与非纤维生成性羰基铁颗粒的作用进行比较。通过Griess反应测定巨噬细胞条件培养基中NO.的稳定氧化产物亚硝酸盐（NO2-）。温石棉（P < 0.01）和青石棉（P < 0.05）石棉纤维（10微克/毫升）均显著增加了AM产生的NO2-。由于已知干扰素-γ（IFN-γ）可诱导巨噬细胞内的NO.合酶，并且由于在石棉工人中已观察到肺内IFN-γ水平升高，因此还在NO.形成的背景下研究了石棉和IFN-γ的联合作用。添加IFN-γ（250至500国际单位/毫升）可协同增强温石棉和青石棉诱导的NO2-形成。值得注意的是，羰基铁对AM产生NO.没有显著影响。NO.合酶抑制剂NG-单甲基-L-精氨酸（0.5至1毫克/毫升）显著减弱了NO2-的产生。相比之下，超氧化物歧化酶（150单位/毫升）显著增强了石棉诱导的AM产生的NO2-（P < 0.001）。由于超氧阴离子可与NO.相互作用生成有毒的羟基自由基，并且由于已知超氧化物歧化酶可预防石棉诱导的损伤，因此石棉纤维诱导的NO.自由基可能代表了一种新的石棉相关损伤形式。
