Mast cell tryptase causes airway smooth muscle hyperresponsiveness in dogs.
Mast cell tryptase causes airway smooth muscle hyperresponsiveness in dogs.
复制标题
肥大细胞类胰蛋白酶会导致狗气道平滑肌高反应性。
DOI：
10.1172/jci113855
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Nadel,JA
中科院分区：
文献类型：
--
作者：
Sekizawa,K;Caughey,GH;Lazarus,SC;Gold,WM;Nadel,JA
狗肥大细胞瘤细胞脱粒获得的上清液大大增加了离体狗支气管平滑肌对组胺的收缩反应的敏感性和幅度。增强的收缩反应完全逆转H1受体拮抗剂，并防止类胰蛋白酶（一种主要的蛋白酶释放组胺从肥大细胞的分泌颗粒）的抑制剂。活性类胰蛋白酶以纯的形式再现组胺诱导的收缩的增强作用。由于组胺和纯化类胰蛋白酶的组合的收缩被取消的Ca 2+通道阻断剂硝苯地平和维拉帕米。KCl和5-羟色胺的支气管收缩作用也被类胰蛋白酶增强，它们与组胺一样，通过主要涉及膜电位依赖性Ca 2+转运的机制收缩气道平滑肌。然而，乙酰胆碱的收缩作用，其收缩犬气道平滑肌的机制独立的钙离子通道，类胰蛋白酶的影响。这些发现表明肥大细胞类胰蛋白酶通过直接或间接作用于Ca 2+通道，显著促进激动剂诱导的支气管平滑肌收缩，因此这些发现提示了犬支气管高反应性的一种新的潜在机制。图片
Supernatants obtained by degranulation of dog mastocytoma cells greatly increased the sensitivity and the magnitude of the contractile response of isolated dog bronchial smooth muscle to histamine. The enhanced contractile response was reversed completely by H1-receptor antagonists and was prevented by an inhibitor of tryptase (a major protease released with histamine from secretory granules of mast cells). The potentiation of histamine-induced contractions was reproduced by active tryptase in pure form. The contractions due to the combination of histamine and purified tryptase were abolished by the Ca2+ channel blockers nifedipine and verapamil. The bronchoconstricting effects of KCl and serotonin, which, like histamine, contract airway smooth muscle by a mechanism predominantly involving membrane potential-dependent Ca2+ transport, were also potentiated by tryptase. However, the contractile effects of acetylcholine, which contracts dog airway smooth muscle by a mechanism independent of Ca2+ channels, were unaffected by tryptase. These findings show a striking promotion of agonist-induced bronchial smooth muscle contraction by mast cell tryptase, via direct or indirect effects on Ca2+ channels, and the findings therefore suggest a novel potential mechanism of hyperresponsiveness in dog bronchi.Images