Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat
Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat
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DOI：
10.1172/jci3169
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发表时间：
1998-07-15
影响因子：
15.9
通讯作者：
Kagan, E
中科院分区：
文献类型：
--
作者：
Tanaka, S;Choe, N;Kagan, E
为了确定是否石棉吸入诱导活性氮物种的形成，三组大鼠间歇性地暴露于2周以上的过滤室内空气（假暴露）或温石棉或青石棉纤维。分别于染毒后1周和6周处死大鼠。在1周时，石棉暴露大鼠的肺泡和胸膜巨噬细胞的数量显着高于假暴露大鼠表现出诱导型一氧化氮合酶蛋白免疫反应性。从石棉暴露大鼠肺泡巨噬细胞也产生显着更大的亚硝酸盐形成比假暴露大鼠的巨噬细胞。强免疫反应性硝基酪氨酸，过氧亚硝酸盐形成的标志物，是显而易见的肺温石棉和青石棉暴露大鼠在1和6周。染色在肺泡管分叉处和细支气管上皮、肺泡巨噬细胞以及内脏和壁胸膜间皮内最明显。假暴露大鼠的肺表现出最低的硝基酪氨酸免疫反应性，显着更大量的硝基酪氨酸检测通过ELISA从石棉暴露大鼠肺提取物比假暴露大鼠。这些结果表明，石棉吸入可以诱导诱导型一氧化氮合酶激活和过氧亚硝酸盐的形成在体内，并提供了一个可能的替代证据：石棉诱导损伤的机制，认为诱导的芬顿反应。to.be
To determine whether asbestos inhalation induces the formation of reactive nitrogen species, three groups of rats were exposed intermittently over 2 wk to either filtered room air (sham-exposed) or to chrysotile or crocidolite asbestos fibers. The rats were killed at 1 or 6 wk after exposure. At 1 wk, significantly greater numbers of alveolar and pleural macrophages from asbestos-exposed rats than from sham-exposed rats demonstrated inducible nitric oxide synthase protein immunoreactivity. Alveolar macrophages from asbestos-exposed rats also generated significantly greater nitrite formation than did macrophages from sham-exposed rats. Strong immunoreactivity for nitrotyrosine, a marker of peroxynitrite formation, was evident in lungs from chrysotile- and crocidolite-exposed rats at 1 and 6 wk. Staining was most evident at alveolar duct bifurcations and within bronchiolar epithelium, alveolar macrophages, and the visceral and parietal pleural mesothelium. Lungs from sham-exposed rats demonstrated minimal immunoreactivity for nitrotyrosine, Significantly greater quantities of nitrotyrosine were detected by ELISA in lung extracts from asbestos-exposed rats than from sham-exposed rats. These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative: mechanism of asbestos-induced injury to that thought to.be induced by Fenton reactions.