Rosenthal G J, Germolec D R, Blazka M E, Corsini E, Simeonova P, Pollock P, Kong L Y, Kwon J, Luster M I
Environmental Immunology and Neurobiology Section, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
J Immunol. 1994 Oct 1;153(7):3237-44.
Studies have indicated that soluble products, including chemotactic factors, released by activated lung macrophages and fibroblasts are critical mediators in the pathogenesis of asbestos-induced pulmonary fibrosis. We provide evidence that mediators produced by lung epithelial cells in response to asbestos may also contribute to lung disease. In the present study, the carcinogenic and fibrogenic fibers, chrysotile and crocidolite asbestos, were shown to directly stimulate the human pulmonary type-II epithelial cell line, A549, and to a lesser degree primary human bronchial epithelial cells, to elicit the chemotactic cytokine IL-8 in the absence of endogenous stimuli such as IL-1 and TNF. That the membrane signaling events responsible for asbestos-induced IL-8 production are distinct from those responsible for IL-8 induction by cytokines was confirmed by using membrane-stabilizing agents and protein synthesis inhibitors. Stimulation was not observed with nonfibrogenic fibers, wollastonite and titanium dioxide, and was the direct result of asbestos-induced initiation of transcription. Asbestos failed to stimulate the release of TNF, IL-1 beta, or monocyte chemoattractant protein-1 in A549 or primary bronchial epithelial cells, indicating that cytokine secretion by asbestos is highly selective. However, a slight release of IL-1 alpha, probably preformed, was released in human bronchial epithelial cells. These data suggest that epithelial cells may, in addition to macrophages and fibroblasts, be an important effector cell in the immunopathogenesis of asbestos-associated diseases and in particular, in the neutrophilic infiltration that is commonly observed after asbestos exposure.
研究表明，活化的肺巨噬细胞和成纤维细胞释放的可溶性产物，包括趋化因子，是石棉诱导的肺纤维化发病机制中的关键介质。我们提供的证据表明，肺上皮细胞对石棉产生的介质也可能导致肺部疾病。在本研究中，致癌和致纤维化纤维，温石棉和青石棉，被证明可直接刺激人肺II型上皮细胞系A549，并在较小程度上刺激原代人支气管上皮细胞，在缺乏内源性刺激（如IL-1和TNF）的情况下引发趋化细胞因子IL-8。通过使用膜稳定剂和蛋白质合成抑制剂证实，负责石棉诱导的IL-8产生的膜信号事件与负责细胞因子诱导IL-8的事件不同。未观察到非致纤维化纤维硅灰石和二氧化钛的刺激作用，且这是石棉诱导转录起始的直接结果。石棉未能刺激A549或原代支气管上皮细胞释放TNF、IL-1β或单核细胞趋化蛋白-1，表明石棉诱导的细胞因子分泌具有高度选择性。然而，人支气管上皮细胞中释放了少量可能预先形成的IL-1α。这些数据表明，除了巨噬细胞和成纤维细胞外上皮细胞可能是石棉相关疾病免疫发病机制中的重要效应细胞，特别是在石棉暴露后常见的中性粒细胞浸润过程中。
