INITIAL PLASMIN-DEGRADATION OF FIBRIN AS THE BASIS OF A POSITIVE FEEDBACK MECHANISM IN FIBRINOLYSIS
INITIAL PLASMIN-DEGRADATION OF FIBRIN AS THE BASIS OF A POSITIVE FEEDBACK MECHANISM IN FIBRINOLYSIS
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DOI：
10.1111/j.1432-1033.1984.tb08132.x
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
THORSEN, S
中科院分区：
文献类型：
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作者：
SUENSON, E;LUTZEN, O;THORSEN, S
研究了纤维蛋白溶解过程中纤维蛋白对[人] Glu-纤溶酶原转化为Glu-纤溶酶的影响。它特别关注由纤溶酶催化的纤维蛋白降解引起的纤维蛋白效应子功能的变化。125 I标记的Glu-纤溶酶原转化为Glu-纤溶酶催化尿激酶或组织纤溶酶原激活剂，在不同的制剂的存在下，逐渐降解的纤维蛋白。Glu-纤溶酶原和纤维蛋白（衍生物）效应物的纤溶酶催化被抑肽酶抑制。完整的纤维蛋白的存在下，增强Glu-纤溶酶的形成率催化的组织型纤溶酶原激活剂，但不是由尿激酶。然而，最初纤溶酶裂解的纤维蛋白的存在下，增加了Glu-纤溶酶形成与两种激活剂，与那些发现与完整的纤维蛋白相比。由纤维蛋白效应物的初始纤溶酶降解诱导的速率增强与其对Glu-纤溶酶原和组织纤溶酶原激活物的亲和力增加相关，表明存在因果关系。尿激酶的弱结合不受纤维蛋白降解的影响，表明效应子功能仅作用于尿激酶激活系统的Glu-纤溶酶原部分。纤维蛋白的进一步降解降低了对Glu-纤溶酶形成的刺激作用。这种减少发生在较早阶段的降解与组织纤溶酶原激活剂比与尿激酶，表明更大的完整性的纤维蛋白效应是必要的，其最佳的相互作用与组织纤溶酶原激活剂比与Glu-纤溶酶原。氨甲环酸饱和低亲和力赖氨酸结合位点的浓度几乎完全解离Glu-纤溶酶原与降解纤维蛋白的结合，但不与完整的纤维蛋白结合。类似于赖氨酸类似物与这些位点的结合，Glu-纤溶酶原的构象可以通过与降解的纤维蛋白结合而改变，从而引起活化速率的增加。
The effect of fibrin on the transformation of [human] Glu-plasminogen to Glu-plasmin during fibrinolysis was studied. It focuses particularly on changes in fibrin effector function caused by plasmin-catalysed fibrin degradation. Conversion of 125I-labeled Glu-plasminogen to Glu-plasmin was catalysed by urokinase or tissue plasminogen activator, in the presence of different preparations of progressively degraded fibrin. Plasmin catalysis of Glu-plasminogen and the fibrin (derivative) effector was inhibited by aprotinin. The presence of intact fibrin enhanced the rate of Glu-plasmin formation catalysed by tissue plasminogen activator, but not by urokinase. The presence of initially plasmin-cleaved fibrin, however, increased the rates of Glu-plasmin formation with both activators, as compared to those found with intact fibrin. The rate enhancements induced by initial plasmin degradation of the fibrin effector was associated with an increase in its affinity to both Glu-plasminogen and tissue plasminogen activator, suggesting causal relationships. The weak binding of urokinase was unaffected by fibrin degradation, indicating that effector function was solely exerted on the Glu-plasminogen moiety of urokinase-activated systems. Further degradation of fibrin decreased the stimulating effect on Glu-plasmin formation. This decrease occurred at an earlier stage of degradation with tissue plasminogen activator than with urokinase, indicating that greater integrity of the fibrin effector is necessary for its optimal interaction with the tissue plasminogen activator than with Glu-plasminogen. Concentrations of tranexamic acid that saturate low-affinity lysine-binding sites nearly completely dissociated the binding of Glu-plasminogen to degraded fibrin, but not to intact fibrin. In analogy with the binding of lysine analogs to these sites, the conformation of Glu-plasminogen may be altered by binding to degraded fibrin, thus giving rise to the increased activation rate.