Moir E, Robbie L A, Bennett B, Booth N A
Department of Medicine & Therapeutics, University of Aberdeen, Institute of Medical Sciences, Scotland, UK.
Thromb Haemost. 2002 Jun;87(6):1006-10.
Polymorphonuclear leucocytes (PMN) are important in the resolution of human thrombi, with u-PA as a key player. We have shown that the u-PA activity of PMN depends on the presence of plasma; the study presented here provides an explanation for that requirement. Here we show that PMN degraded scu-PA and also tcu-PA, t-PA and plasmin, resulting in loss of fibrinolytic activity. Plasma protected against this degradation; alpha1-antitrypsin was identified as a protective factor. Purified human neutrophil elastase mirrored the effects of PMN, again neutralized by plasma inhibitors. These findings illustrate the dual role of PMN in the breakdown of thrombi, in that they contribute both u-PA, which lyses fibrin, and other proteases, including elastase, which can cleave fibrin and plasminogen activators/plasmin. Similarly, plasma can potentiate fibrinolysis by neutralization of PMN elastase, in addition to direct inhibition of fibrinolytic proteases. Our previous studies show that PMN in thrombi are mostly pro-fibrinolytic; the anti-fibrinolytic role defined here may be important in other pathologies where fibrin persists.
多形核白细胞（PMN）在人类血栓溶解过程中起着重要作用，尿激酶型纤溶酶原激活剂（u-PA）是关键因素。我们已经表明，PMN的u-PA活性取决于血浆的存在；此处呈现的研究为这一需求提供了解释。在这里，我们表明PMN可降解单链尿激酶型纤溶酶原激活剂（scu-PA）以及双链尿激酶型纤溶酶原激活剂（tcu-PA）、组织型纤溶酶原激活剂（t-PA）和纤溶酶，导致纤溶活性丧失。血浆可防止这种降解；α1-抗胰蛋白酶被确定为一种保护因子。纯化的人中性粒细胞弹性蛋白酶反映了PMN的作用，同样被血浆抑制剂中和。这些发现说明了PMN在血栓分解中的双重作用，即它们既提供溶解纤维蛋白的u-PA，也提供其他蛋白酶，包括可裂解纤维蛋白和纤溶酶原激活剂/纤溶酶的弹性蛋白酶。同样，血浆除了直接抑制纤溶蛋白酶外，还可通过中和PMN弹性蛋白酶来增强纤溶作用。我们之前的研究表明，血栓中的PMN大多具有促纤溶作用；此处定义的抗纤溶作用在纤维蛋白持续存在的其他病理情况下可能很重要。
