Stief T W
Thrombosis and Hemostasis Section, University Hospital Seville, Spain.
Blood Coagul Fibrinolysis. 1993 Feb;4(1):117-21.
Activated phagocytes participate in physiological thrombolysis producing non-radical excited oxidants and the important proteases elastase and urokinase. The interaction of oxidized fibrin with the proteases of the fibrinolytic system is therefore physiologically relevant. Here it is shown that human pro-urokinase is activated three- to four-fold faster in the presence of an oxidized solid fibrin matrix. In contrast, oxidized fibrin did not favour the fibrinolytic activity of urokinase or t-PA. Measurement of urokinase antigen showed that urokinase bound slightly to strongly oxidized denatured fibrin, whereas pro-urokinase did not. Plasmin degraded oxidized fibrin more rapidly than non-oxidized fibrin. Thus, singlet molecular oxygen (1O2) converts fibrin to a form that stimulates the activation of plasminogen (bound to oxidized fibrin) by pro-urokinase and that of pro-urokinase by plasmin. The oxidative modification of fibrin by 1O2 is specific. In contrast to oxygen radicals (H2O2 in high concentration) 1O2 does not directly destroy protein chains but favours subsequent fibrinolysis. Thus 1O2 prepares fibrin for its specific degradation.
活化的吞噬细胞参与生理性溶栓过程，产生非自由基活性氧化剂以及重要的蛋白酶——弹性蛋白酶和尿激酶。因此，氧化纤维蛋白与纤维蛋白溶解系统蛋白酶之间的相互作用具有生理相关性。本文表明，在存在氧化固体纤维蛋白基质的情况下，人尿激酶原的活化速度快三到四倍。相比之下，氧化纤维蛋白并不利于尿激酶或组织型纤溶酶原激活剂（t-PA）的纤维蛋白溶解活性。尿激酶抗原的测定表明，尿激酶与强氧化变性纤维蛋白有轻微结合，而尿激酶原则没有。纤溶酶降解氧化纤维蛋白的速度比未氧化纤维蛋白更快。因此，单线态分子氧（1O2）将纤维蛋白转化为一种形式，该形式可刺激尿激酶原激活与氧化纤维蛋白结合的纤溶酶原，以及纤溶酶激活尿激酶原。1O2对纤维蛋白的氧化修饰具有特异性。与氧自由基（高浓度的H2O2）不同，1O2不会直接破坏蛋白质链，而是有利于随后的纤维蛋白溶解。因此，1O2使纤维蛋白为其特异性降解做好准备。
