Gouin I, Lecompte T, Morel M C, Lebrazi J, Modderman P W, Kaplan C, Samama M M
Laboratoire Central d'Hématologie, Hopital Hôtel Dieu, Paris, France.
Circulation. 1992 Mar;85(3):935-41. doi: 10.1161/01.cir.85.3.935.
Plasmin has been reported both to activate platelets and to inhibit platelet functions. The latter effect was thought to be caused by proteolysis of the main membrane glycoproteins.
We found that incubation of citrated human platelet-rich plasma with streptokinase (SK) (300 IU/ml) does not produce any detectable activation but leads to a time-dependent inhibition of ADP-induced aggregation accompanied by substantial fibrinogenolysis. These effects were abrogated by previous addition of a plasmin inhibitor, aprotinin. Crossover experiments (SK-treated or control platelets mixed with SK-treated or control plasma) demonstrated that the platelets remained functional and that the aggregation defect was caused by fibrinogenolysis. Further experiments (addition of purified fibrinogen to fibrinogen-depleted plasma with either SK or thrombin) suggested that in addition to the low residual level of fibrinogen, fibrinogen degradation products had an inhibitory effect. Under the same conditions, tissue-type plasminogen activator (t-PA) (3,000 ng/ml) had no effect on platelet aggregation, and plasma fibrinogen was not significantly lowered. The effects on glycoproteins IIb-IIIa of incubation with SK, t-PA, or plasmin were assessed with immunoblots with murine monoclonal antibodies directed against either part of the complex, which is the receptor for fibrinogen. Proteolysis was detected only in the presence of EDTA, a potent chelator of divalent cations.
The incubation of human platelets in citrated plasma with SK concentrations obtained during therapy leads to an aggregation defect that is related to the decrease in fibrinogen, the adhesive protein involved in this function, and to the impeding effect of fibrinogen degradation products on its binding onto platelets but not to an alteration of the corresponding platelet receptor, the heterodimer glycoproteins IIb-IIIa.
有报道称纤溶酶既能激活血小板，又能抑制血小板功能。后一种作用被认为是由主要膜糖蛋白的蛋白水解所致。
我们发现，将枸橼酸化的富含人血小板血浆与链激酶（SK）（300 IU/ml）一起孵育不会产生任何可检测到的激活作用，但会导致对ADP诱导的聚集产生时间依赖性抑制，并伴有大量纤维蛋白原溶解。预先添加纤溶酶抑制剂抑肽酶可消除这些作用。交叉实验（SK处理的或对照血小板与SK处理的或对照血浆混合）表明血小板仍保持功能，且聚集缺陷是由纤维蛋白原溶解引起的。进一步的实验（向纤维蛋白原耗尽的血浆中添加纯化的纤维蛋白原以及SK或凝血酶）表明，除了纤维蛋白原的低残留水平外，纤维蛋白原降解产物也有抑制作用。在相同条件下，组织型纤溶酶原激活剂（t-PA）（3000 ng/ml）对血小板聚集无影响，血浆纤维蛋白原也未显著降低。用针对该复合物任一部位（即纤维蛋白原受体）的鼠单克隆抗体进行免疫印迹，评估与SK、t-PA或纤溶酶孵育对糖蛋白IIb-IIIa的影响。仅在存在二价阳离子的强效螯合剂EDTA的情况下检测到蛋白水解。
在枸橼酸血浆中，将人血小板与治疗期间获得的SK浓度一起孵育会导致聚集缺陷，这与纤维蛋白原（参与此功能的黏附蛋白）的减少以及纤维蛋白原降解产物对其与血小板结合的阻碍作用有关，而与相应的血小板受体（异二聚体糖蛋白IIb-IIIa）的改变无关。
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