Choe N, Tanaka S, Xia W, Hemenway D R, Roggli V L, Kagan E
Department of Pathology, Uniformed Services University of the Health Sciences, F. Edward Hébert School of Medicine, Bethesda, MD 20814-4799, USA.
Environ Health Perspect. 1997 Sep;105 Suppl 5(Suppl 5):1257-60. doi: 10.1289/ehp.97105s51257.
The pathogenesis of asbestos-induced pleural fibrosis is poorly understood. Moreover, there has been a long-standing controversy regarding the relative potential of different commercial types of asbestos to cause pleural disease. We postulated that inhaled asbestos fibers translocate to the pleural space where they stimulate the recruitment and activation of pleural macrophages. To test this hypothesis, and to determine whether there are differences between inhaled amphibole and serpentine asbestos, Fischer 344 rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 2 weeks) to either National Institute of Environmental Health Sciences (NIEHS) crocidolite (average concentration 7.55 mg/m3) or NIEHS chrysotile fibers (average concentration 8.51 mg/m3). Comparisons were made with sham-exposed rats. The rats were sacrificed at 1 and 6 weeks after the cessation of exposure. More pleural macrophages were recovered at 1 and 6 weeks after crocidolite and chrysotile exposure than after sham exposure. Small numbers of crocidolite fibers (approximately 1 per 4000 cells) were detected in the pleural cell pellet of one crocidolite-exposed rat by scanning electron microscopy. Pleural macrophage supernatants were assayed for production of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF-alpha) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF-alpha were generated by pleural macrophages at 1 and 6 weeks after either crocidolite or chrysotile inhalation than after sham exposure. Conceivably, translocation of asbestos fibers to the pleural space may provide a stimulus for persistent pleural space inflammation, cytokine production, and the generation of toxic oxygen and nitrogen radicals. Enhanced cytokine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constituents by pleural mesothelial cells. Thus, our findings may have significance for the development of asbestos-induced pleural injury.
石棉所致胸膜纤维化的发病机制目前尚不清楚。此外，对于不同商业类型的石棉导致胸膜疾病的相对可能性，长期以来一直存在争议。我们推测，吸入的石棉纤维转移至胸膜腔，在那里它们刺激胸膜巨噬细胞的募集和活化。为了验证这一假设，并确定吸入的闪石类石棉和蛇纹石类石棉之间是否存在差异，将Fischer 344大鼠通过间歇性吸入（每天6小时，每周5天，共2周）暴露于美国国立环境卫生科学研究所（NIEHS）的青石棉（平均浓度7.55毫克/立方米）或NIEHS温石棉纤维（平均浓度8.51毫克/立方米）。将其与假暴露大鼠进行比较。在暴露停止后1周和6周处死大鼠。与假暴露相比，青石棉和温石棉暴露后1周和6周回收的胸膜巨噬细胞更多。通过扫描电子显微镜在一只青石棉暴露大鼠的胸膜细胞沉淀中检测到少量青石棉纤维（每4000个细胞中约有1根）。检测胸膜巨噬细胞上清液中一氧化氮（NO）的产生（通过格里斯反应）和肿瘤坏死因子α（TNF-α）（通过酶联免疫吸附测定法）。与假暴露相比，青石棉或温石棉吸入后1周和6周胸膜巨噬细胞产生的NO以及TNF-α明显更多。可以想象，石棉纤维转移至胸膜腔可能会刺激胸膜腔持续炎症、细胞因子产生以及有毒氧和氮自由基的生成。胸膜腔内细胞因子分泌增加可能进而上调胸膜间皮细胞黏附分子的表达和细胞外基质成分的合成。因此，我们的研究结果可能对石棉所致胸膜损伤的发生具有重要意义。
