Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs
Platelet activation induces cell-surface immunoreactive tissue factor expression, which is modulated differently by antiplatelet drugs
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DOI：
10.1161/01.atv.0000085629.23209.aa
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发表时间：
2003-09-01
影响因子：
8.7
通讯作者：
Tremoli, E
中科院分区：
文献类型：
--
作者：
Camera, M;Frigerio, M;Tremoli, E
组织因子（TF）是生理和病理条件下发生的凝血级联反应的主要激活剂。最近的数据表明，人血小板可能含有TF，可能来自白细胞。在这项研究中，我们研究了血小板内TF是否可以通过血小板激动剂暴露在膜上。调制这个过程中的抗血小板药物已被evaluated，以及.Methods和Results-流式细胞术分析未刺激的血小板显示少量的膜相关免疫反应性TF（irTF）在全血中，血小板丰富的血浆，和洗涤血小板分离健康受试者。ADP，凝血酶受体激活肽，肾上腺素显着增加功能活性，膜相关irTF。ADP诱导irTF暴露的浓度和时间依赖性的方式。激动剂诱导的irTF表达被伊洛前列素完全抑制，但不被阿司匹林抑制。有趣的是，糖蛋白IIb/IIIa拮抗剂没有抑制，而是加强ADP对血小板irTF表达的刺激作用。实时聚合酶链反应实验表明，TF mRNA在未刺激的platelet. Conclusions，这些研究结果表明，血小板激动剂和抗血小板药物可能会调节血小板相关的irTF表达的检测量。调节TF表达确立了血小板通过凝血介导的机制在维持血栓形成和生长中先前未被认识到的作用的可能性。
Objective-Tissue factor (TF) is the main activator of the coagulation cascade occurring in physiologic and pathologic conditions. Recent data suggest that human platelets might contain TF that is possibly derived from leukocytes. In this study, we investigated whether intraplatelet TF can be exposed on the membrane by platelet agonists. The modulation of this process by antiplatelet drugs has been evaluated as well.Methods and Results-Flow cytometric analysis of unstimulated platelets showed a small amount of membrane-associated immunoreactive TF (irTF) in whole blood, platelet-rich plasma, and washed platelets isolated from healthy subjects. ADP, thrombin receptor-activating peptide, and epinephrine significantly increased functionally active, membrane-associated irTF. ADP induced irTF exposure in a concentration- and time-dependent fashion. Agonist-induced irTF expression was completely inhibited by iloprost but not by aspirin. Interestingly, glycoprotein IIb/IIIa antagonists did not inhibit but rather potentiated the stimulatory effect of ADP on platelet irTF expression. Real-time polymerase chain reaction experiments showed detectable amounts of TF mRNA in unstimulated platelets.Conclusions-These findings indicate that platelet agonists and antiplatelet drugs might modulate platelet-associated irTF expression. Regulated TF expression establishes the potential for a previously unrecognized role for platelets in sustaining thrombus formation and growth via coagulation-mediated mechanisms.