INHIBITION BY HEPARIN OF PLATELET ACTIVATION INDUCED BY NEUTROPHIL-DERIVED CATHEPSIN-G
INHIBITION BY HEPARIN OF PLATELET ACTIVATION INDUCED BY NEUTROPHIL-DERIVED CATHEPSIN-G
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DOI：
10.1016/0014-2999(92)90437-9
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发表时间：
1992-06-17
影响因子：
5
通讯作者：
CERLETTI, C
中科院分区：
文献类型：
--
作者：
EVANGELISTA, V;PICCARDONI, P;CERLETTI, C
肝素是预防和治疗血栓形成最广泛使用的抗凝药物。然而，抑制凝血可能不能完全解释这种药物的抗血栓活性。本研究表明，不同的肝素制剂（50 nM）完全阻止纯化的中性粒细胞来源的组织蛋白酶G （E.C. No. 3.4.21.20）诱导的人血小板聚集、血清素释放和血栓素B2的产生。这种抑制作用与化合物的抗凝血特性无关，因为具有抗凝血酶III灭活活性位点的肝素制剂也有效。肝素在相同浓度范围内抑制酶的蛋白酶活性。由于组织蛋白酶G对血小板的作用需要完整的蛋白水解活性位点，因此药物对组织蛋白酶G诱导的血小板活化的抑制作用可能是通过阻断蛋白酶活性来解释的。肝素还可降低混合细胞悬液中活化的多形核白细胞释放的组织蛋白酶G诱导的血小板活化。由于多形核白细胞可能通过释放组织蛋白酶G诱导血小板活化而导致动脉和静脉血栓形成，因此肝素的这一新特性可用于优化其抗血栓疗效。
Heparin is the most widely used anticoagulant drug for prevention and treatment of thrombosis. However, inhibition of blood coagulation might not fully explain the antithrombotic activity of this drug. The present study shows that different heparin preparations (50 nM) completely prevent human platelet aggregation, serotonin release and thromboxane B2 production induced by purified neutrophil-derived cathepsin G (E.C. No. 3.4.21.20). This inhibitory effect was not related to the anticoagulant property of the compounds, since a heparin preparation with an inactivated active site for antithrombin III was also effective. Heparins inhibited the protease activity of the enzyme over the same range of concentrations. Since the effect of cathepsin G on platelets requires an intact proteolytic active site, the inhibitory effect of the drugs on cathepsin G-induced platelet activation may be explained by a blockade of protease activity. Heparins were also shown to reduce platelet activation induced by cathepsin G released from activated polymorphonuclear leucocytes in mixed cell suspensions. As polymorphonuclear leucocytes might contribute to both arterial and venous thrombosis through platelet activation induced by the release of cathepsin G, this novel property of heparin could be used to optimize its antithrombotic efficacy.