A protective role for protease-activated receptors in the airways
A protective role for protease-activated receptors in the airways
复制标题
DOI：
10.1038/18223
复制
发表时间：
1999-03-11
期刊：
影响因子：
64.8
通讯作者：
Moffatt, JD
中科院分区：
文献类型：
--
作者：
Cocks, TM;Fong, B;Moffatt, JD
保护上肠细胞免受胰蛋白酶消化的作用依赖于前列腺素类前列腺素E-2（PGE（2）），并由上皮细胞中的蛋白酶激活受体介导（1，2）。由于气道上皮在形态上相似，并且也表达这些受体之一，PAR 2（参考文献3），是PGE 2的主要来源（参考文献4），我们推断支气管上皮PAR 2也可能参与气道中的前列腺素依赖性细胞保护。在此，我们表明PAR 2的激活，其与气道上皮中的胰蛋白酶（原）化学共定位，通过从上皮释放环加氧酶产物，导致小鼠、大鼠、豚鼠和人的气道制备物松弛。在离体气道中的这种生理保护反应也发生在麻醉大鼠中，其中PAR 2的激活导致支气管收缩的显著和延长的抑制。PAR 2脱敏后，对胰蛋白酶的反应通过依赖于蛋白质从头合成和运输的机制迅速恢复。我们的研究结果表明，从上皮释放的胰蛋白酶可以通过激活上皮PAR 2在气道中启动强大的支气管保护作用。
The protection of cells in the upper intestine against digestion by pancreatic trypsin depends on the prostanoid prostaglandin E-2 (PGE(2)) and is mediated by protease-activated receptors in the epithelium(1,2). As the airway epithelium is morphologically similar and also expresses one of these receptors, PAR2 (ref. 3), and is a major source of PGE2 (ref. 4), we reasoned that bronchial epithelial PAR2 might also participate in prostanoid-dependent cytoprotection in the airways, Here we show that activation of PAR2, which co-localizes immunohistochemically with trypsin(ogen) in airway epithelium, causes the relaxation of airway preparations from mouse, rat, guinea-pig and humans by the release of a cyclooxygenase product from the epithelium.This physiological protective response in isolated airways also occurred in anaesthetized rats, where activation of PAR2 caused a marked and prolonged inhibition of bronchoconstriction. After desensitization of PAR2, the response to trypsin recovered rapidly by mechanisms dependent on de novo synthesis and trafficking of proteins. Our results indicate that trypsin released from the epithelium can initiate powerful bronchoprotection in the airways by activation of epithelial PAR2.