Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness.
Extravascular fibrin, plasminogen activator, plasminogen activator inhibitors, and airway hyperresponsiveness.
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DOI：
10.1172/jci19569
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发表时间：
2004-07
期刊：
影响因子：
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通讯作者：
S. Wagers;Ryan J. Norton;L. Rinaldi;J. Bates;B. Sobel;C. Irvin
中科院分区：
文献类型：
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作者：
S. Wagers;Ryan J. Norton;L. Rinaldi;J. Bates;B. Sobel;C. Irvin
呼吸道高反应性的潜在机制尚未完全阐明。呼吸道炎症的表现之一是多种血浆蛋白渗入气道腔。它们包括纤维蛋白原和凝血酶。凝血酶分解纤维蛋白原形成纤维蛋白，纤维蛋白是血栓的主要成分。纤维蛋白使表面活性物质失活。呼吸道表面的表面活性物质通过降低表面张力来维持呼吸道通畅。在这项研究中，免疫组织化学检测了一名死于哮喘持续状态的患者和诱发过敏性呼吸道炎症的小鼠的远端气道管腔表面的纤维蛋白。此外，我们观察到过敏性气道炎小鼠的气道纤溶系统蛋白平衡改变与促进纤维蛋白沉积是一致的。将小鼠的呼吸道暴露于雾化纤维蛋白原、凝血酶或纤维蛋白原和凝血酶。与对照组相比，只有纤维蛋白原和凝血酶引起的气道高反应性。一种雾化纤溶剂，组织型纤溶酶原激活剂，显著降低过敏性呼吸道炎症小鼠的气道高反应性。这些结果与纤维蛋白原和凝血酶的渗漏以及它们在呼吸道表面的积聚在呼吸道高反应性的发病机制中的假说是一致的。
Mechanisms underlying airway hyperresponsiveness are not yet fully elucidated. One of the manifestations of airway inflammation is leakage of diverse plasma proteins into the airway lumen. They include fibrinogen and thrombin. Thrombin cleaves fibrinogen to form fibrin, a major component of thrombi. Fibrin inactivates surfactant. Surfactant on the airway surface maintains airway patency by lowering surface tension. In this study, immunohistochemically detected fibrin was seen along the luminal surface of distal airways in a patient who died of status asthmaticus and in mice with induced allergic airway inflammation. In addition, we observed altered airway fibrinolytic system protein balance consistent with promotion of fibrin deposition in mice with allergic airway inflammation. The airways of mice were exposed to aerosolized fibrinogen, thrombin, or to fibrinogen followed by thrombin. Only fibrinogen followed by thrombin resulted in airway hyperresponsiveness compared with controls. An aerosolized fibrinolytic agent, tissue-type plasminogen activator, significantly diminished airway hyperresponsiveness in mice with allergic airway inflammation. These results are consistent with the hypothesis that leakage of fibrinogen and thrombin and their accumulation on the airway surface can contribute to the pathogenesis of airway hyperresponsiveness.