Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells
Surface-retained tPA is essential for effective fibrinolysis on vascular endothelial cells
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DOI：
10.1182/blood-2011-05-353912
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发表时间：
2011-09-15
期刊：
影响因子：
20.3
通讯作者：
Urano, Tetsumei
中科院分区：
文献类型：
--
作者：
Suzuki, Yuko;Yasui, Hideki;Urano, Tetsumei
在之前的研究中，我们证明了组织纤溶酶原激活剂（tPA）独特的分泌动力学，其中tPA在血管内皮细胞分泌颗粒的胞吐作用后以重链依赖性方式保留在细胞表面。在这里，我们研究了保留的 tPA 如何表达其酶活性。保留的tPA有效增加了细胞表面和细胞周区域赖氨酸结合位点依赖性纤溶酶原的结合；这是通过抑制 tPA 或纤溶酶的酶活性而消除的，这表明作为表面/细胞周蛋白被纤溶酶降解的结果，羧基末端赖氨酸的从头生成是必要的。保留的 tPA 引发血管内皮细胞上形成的纤维蛋白网络的区域性凝块溶解，随后纤溶酶原与溶解前沿结合。我们的结果证明，分泌和保留的 tPA 对于维持血管内皮细胞表面的高纤溶活性和有效的血栓溶解至关重要。 （血。2011；118（11）：3182-3185）
In a previous study, we demonstrated unique secretory dynamics of tissue plasminogen activator (tPA) in which tPA was retained on the cell surface in a heavy chain-dependent manner after exocytosis from secretory granules in vascular endothelial cells. Here, we examined how retained tPA expresses its enzymatic activity. Retained tPA effectively increased the lysine binding site-dependent binding of plasminogen on the cell surface and pericellular area; this was abolished by inhibition of enzymatic activity of either tPA or plasmin, which suggests that de novo generation of carboxyl-terminal lysine as a consequence of degradation of surface/pericellular proteins by plasmin is essential. Retained tPA initiated zonal clot lysis of a fibrin network that had been formed on vascular endothelial cells, which was preceded by the binding of plasminogen to the lysis front. Our results provide evidence that secreted and retained tPA is essential for maintaining both high fibrinolytic activity and effective clot lysis on the vascular endothelial cell surface. (Blood. 2011;118(11): 3182-3185)