Secretion and antifibrinolytic function of thrombin‐activatable fibrinolysis inhibitor from human platelets
Secretion and antifibrinolytic function of thrombin‐activatable fibrinolysis inhibitor from human platelets
复制标题
人血小板凝血酶激活纤溶抑制剂的分泌和抗纤溶功能
DOI：
10.1111/j.1538-7836.2010.04024.x
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发表时间：
2010
影响因子：
10.4
通讯作者：
M. Boffa
中科院分区：
文献类型：
--
作者：
S. L. Schadinger;Joellen H. H. Lin;M. Garand;M. Boffa
总结。背景：凝血酶活化纤维蛋白溶解抑制剂（TAFI）是一种首先在人血浆中发现的酶原，它通过凝血酶、凝血酶与凝血调节蛋白复合物或纤溶酶的蛋白水解裂解而被激活。活性TAFI通过从部分降解的纤维蛋白中去除C端赖氨酸残基来减弱纤维蛋白溶解，从而抑制纤维蛋白溶解级联中的一个有效的正反馈回路。在血小板中存在一个单独的TAFI池。目的和方法：我们的目的是确认TAFI存在于洗净的凝血酶刺激的血小板培养基中，并通过western blot分析和激活TAFI的定量分析来评估血小板TAFI的特征。我们还评估了血小板TAFI在体外抑制纤维蛋白溶解的能力，使用富含血小板的血栓溶解试验。结果：我们的数据与静息血小板α -颗粒中TAFI的存在一致。与之前的报道相反，血小板TAFI与血浆来源的TAFI在电泳迁移率方面非常相似。我们也首次表明，血小板来源的TAFI能够在体外独立于血浆TAFI的情况下减弱富含血小板的血栓溶解。此外，我们证明了血小板来源的TAFI和血浆中存在的TAFI对溶栓的叠加效应。结论：综上所述，这些观察结果表明，血小板来源的TAFI的分泌可以增加血浆中已经存在的TAFI浓度，从而增强纤溶级联的衰减。这在血管损伤或病理性血栓形成的区域可能是显著的，在那里活化的血小板已知积累。
Summary. Background: The thrombin‐activatable fibrinolysis inhibitor (TAFI) is a zymogen first characterized in human plasma that is activated through proteolytic cleavage by thrombin, thrombin in complex with thrombomodulin, or plasmin. Active TAFI attenuates fibrinolysis by removing C‐terminal lysine residues from partially degraded fibrin, thereby inhibiting a potent positive feedback loop in the fibrinolytic cascade. The existence of a separate pool of TAFI within platelets has been described. Objectives and Methods: We aimed to confirm the presence of TAFI in the medium of washed, thrombin‐stimulated platelets and to evaluate the characteristics of platelet TAFI by western blot analysis and with a quantitative assay for activated TAFI. We also assessed the ability of platelet TAFI to inhibit fibrinolysis in vitro, using a platelet‐rich thrombus lysis assay. Results: Our data are consistent with the presence of TAFI in the α‐granules of resting platelets. In contrast to previous reports, platelet TAFI is very similar in electrophoretic mobility to plasma‐derived TAFI. We also show, for the first time, that platelet‐derived TAFI is capable of attenuating platelet‐rich thrombus lysis in vitro independently of plasma TAFI. Moreover, we demonstrate additive effects on thrombolysis of platelet‐derived TAFI and TAFI present in plasma. Conclusions: Taken together, these observations indicate that the secretion of platelet‐derived TAFI can augment the concentrations of TAFI already present in plasma to enhance attenuation of the fibrinolytic cascade. This could be significant in regions of vascular damage or pathologic thrombosis, where activated platelets are known to accumulate.