Lijnen H R, Collen D
Center for Molecular and Vascular Biology, K.U. Leuven, Belgium.
Baillieres Clin Haematol. 1995 Jun;8(2):277-90. doi: 10.1016/s0950-3536(05)80268-9.
The fibrinolytic system comprises an inactive proenzyme, plasminogen, that is converted by plasminogen activators to the active enzyme, plasmin, which degrades fibrin. Two immunologically distinct plasminogen activators (PA) have been identified: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). t-PA mediated plasminogen activation is mainly involved in the dissolution of fibrin in the circulation, whereas u-PA mediated plasminogen activation mainly plays a role in pericellular proteolysis. Plasminogen activation is regulated by specific molecular interactions between its main components, such as binding of plasminogen and t-PA to fibrin, or to specific cellular receptors resulting in enhanced plasminogen activation, inhibition of t-PA and u-PA by plasminogen activator inhibitors (PAI) and inhibition of plasmin by alpha 2-antiplasmin. Controlled synthesis and release of PAs and PAIs primarily from endothelial cells also contributes to the regulation of physiological fibrinolysis. The lysine binding sites situated in the kringle structures of plasminogen play a crucial role in the regulation of fibrinolysis by modulating its binding to fibrin and to cell surfaces, and by controlling the inhibition rate of plasmin by alpha 2-antiplasmin.
纤维蛋白溶解系统包括一种无活性的前体酶，即纤溶酶原，它被纤溶酶原激活剂转化为活性酶纤溶酶，纤溶酶可降解纤维蛋白。已鉴定出两种免疫性质不同的纤溶酶原激活剂（PA）：组织型纤溶酶原激活剂（t-PA）和尿激酶型纤溶酶原激活剂（u-PA）。t-PA介导的纤溶酶原激活主要参与循环中纤维蛋白的溶解，而u-PA介导的纤溶酶原激活主要在细胞周围蛋白水解中起作用。纤溶酶原激活受其主要成分之间特定分子相互作用的调节，例如纤溶酶原和t-PA与纤维蛋白或特定细胞受体的结合，导致纤溶酶原激活增强，纤溶酶原激活剂抑制剂（PAI）对t-PA和u-PA的抑制以及α2-抗纤溶酶对纤溶酶的抑制。主要来自内皮细胞的PA和PAI的受控合成和释放也有助于生理性纤维蛋白溶解的调节。位于纤溶酶原kringle结构中的赖氨酸结合位点在纤维蛋白溶解的调节中起关键作用，通过调节其与纤维蛋白和细胞表面的结合，并通过控制α2-抗纤溶酶对纤溶酶的抑制率。
