Lu H, Soria C, Li H, Soria J, Lijnen H R, Perrot J Y, Caen J P
INSERM U 150, Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France.
Thromb Haemost. 1991 Jan 23;65(1):67-72.
Previous studies have shown that plasmin can activate platelets and can also disperse platelet aggregates by degradation of fibrinogen bound to platelets. In this study, the role of the active center and the lysine binding sites (LBS) of human plasmin in activating platelets and in dispersing platelet aggregates is investigated using aprotinin and the tripeptide Val-Phe-Lys-CH2Cl to inhibit the active center and using epsilon-aminocaproic acid (EACA) to specifically block the LBS. Our results show that the catalytic activity of plasmin is indispensable both for activating platelets and for dispersing platelet aggregates. Binding of plasmin to platelets through the LBS enhances its activating potential, since both EACA (1 mM) and Lys-plasminogen (molar ratio of plasminogen:plasmin at 2:1 to 4:1) inhibit plasmin-induced platelet activation, whereas Glu-plasminogen at a molar ratio of 15:1 had no effect. Furthermore, plasmin which lacks the LBS (miniplasmin), is about 3 fold less effective in activating platelets. However, plasmin binding through the LBS is not absolutely required to disperse platelet aggregates, since EACA at 30 mmol/l was unable to prevent disaggregation by plasmin (half disaggregation time: 40 min in the presence of EACA against 27 min in its absence). It also appeared that fibrinogen receptors on activated platelets are resistant to plasmin degradation, and that disaggregation of plasmin-induced platelet aggregates was much slower than the degradation of fibrinogen by plasmin.
先前的研究表明，纤溶酶可激活血小板，还可通过降解与血小板结合的纤维蛋白原使血小板聚集体分散。在本研究中，使用抑肽酶和三肽缬氨酸-苯丙氨酸-赖氨酸-二氯甲烷抑制人纤溶酶的活性中心，并使用ε-氨基己酸（EACA）特异性阻断赖氨酸结合位点（LBS），研究人纤溶酶的活性中心和LBS在激活血小板及使血小板聚集体分散中的作用。我们的结果表明，纤溶酶的催化活性对于激活血小板和使血小板聚集体分散均不可或缺。纤溶酶通过LBS与血小板的结合增强了其激活潜能，因为EACA（1 mM）和赖氨酸纤溶酶原（纤溶酶原与纤溶酶的摩尔比为2:1至4:1）均可抑制纤溶酶诱导的血小板激活，而摩尔比为15:1的谷氨酸纤溶酶原则无此作用。此外，缺乏LBS的纤溶酶（微型纤溶酶）激活血小板的效力约低3倍。然而，通过LBS的纤溶酶结合对于使血小板聚集体分散并非绝对必需，因为30 mmol/l的EACA无法阻止纤溶酶引起的解聚（半数解聚时间：存在EACA时为40分钟，不存在时为27分钟）。还发现激活的血小板上的纤维蛋白原受体对纤溶酶降解具有抗性，且纤溶酶诱导的血小板聚集体的解聚比纤溶酶对纤维蛋白原的降解要慢得多。
