Increased phosphorylated extracellular signal-regulated kinase immunoreactivity associated with proliferative and morphologic lung alterations after chrysotile asbestos inhalation in mice.
Increased phosphorylated extracellular signal-regulated kinase immunoreactivity associated with proliferative and morphologic lung alterations after chrysotile asbestos inhalation in mice.
复制标题
小鼠吸入温石棉后，磷酸化细胞外信号调节激酶免疫反应性增加与肺增殖和形态学改变相关。
DOI：
10.1016/s0002-9440(10)65001-8
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Mossman,BT
中科院分区：
文献类型：
--
作者：
Robledo,RF;Buder-Hoffmann,SA;Cummins,AB;Walsh,ES;Taatjes,DJ;Mossman,BT
细胞外信号调节激酶（ERK）的激活与石棉相关的细胞凋亡和增殖的出现在间皮瘤和肺泡上皮细胞，并可能与肺纤维化的发展。本研究的目的是描述暴露于石棉的C57 Bl/6小鼠中炎症、细胞增殖和纤维化的发展与ERK磷酸化模式的关系。石棉暴露10天和20天后发生炎症，支气管肺泡灌洗液中总蛋白和中性粒细胞增加证明了这一点。在第30天时，在细支气管上皮细胞中观察到细胞增殖增加，在第4、14和30天时，在肺的肺泡隔室中观察到细胞增殖增加。在肺羟脯氨酸或前胶原mRNA水平没有升高的情况下，30天时出现肺纤维化的三色阳性局灶性病变。吸入14天和30天后，在纤维化病变部位的肺上皮细胞内观察到ERK磷酸化显着增加。除了表征小鼠吸入石棉肺模型，我们提供的第一个证据表明，在体内肺上皮细胞内的ERK信号转导的激活，吸入石棉纤维。
Activation of extracellular signal-regulated kinases (ERK) has been associated with the advent of asbestos-associated apoptosis and proliferation in mesothelial and alveolar epithelial cells and may be linked to the development of pulmonary fibrosis. The objective of studies here was to characterize the development of inflammation, cellular proliferation, and fibrosis in asbestos-exposed C57Bl/6 mice in relationship to patterns of ERK phosphorylation. Inflammation occurred after 10 and 20 days of asbestos exposure as evidenced by increases in total protein and neutrophils in bronchoalveolar lavage fluid. Increases in cell proliferation were observed at 30 days in bronchiolar epithelia and at 4, 14, and 30 days in the alveolar compartment of the lung. Trichrome-positive focal lesions of pulmonary fibrosis developed at 30 days in the absence of elevations in lung hydroxyproline or procollagen mRNA levels. Striking increases in ERK phosphorylation were observed within pulmonary epithelial cells at sites of developing fibrotic lesions after 14 and 30 days of inhalation. In addition to characterizing a murine inhalation model of asbestosis, we provide the first evidence showing activation of ERK signaling within lung epithelium in vivo, following inhalation of asbestos fibers.