Vallés Juana, Santos M Teresa, Aznar Justo, Martínez Marcial, Moscardó Antonio, Piñón Marta, Broekman M Johan, Marcus Aaron J
Research Center and Department of Clinical Pathology, University Hospital La Fe, Valencia, Spain.
Blood. 2002 Jun 1;99(11):3978-84. doi: 10.1182/blood.v99.11.3978.
Activated platelets release biologically active compounds, which then recruit additional platelets into an evolving thrombus. We studied activation of alpha(IIb)beta(3) and exposure of P-selectin on platelets recruited by releasates obtained from collagen-treated platelets and evaluated modifications in prothrombotic effects of releasates induced by platelet-erythrocyte interactions and aspirin treatment. Releasates from collagen-stimulated platelets induced alpha(IIb)beta(3) activation and P-selectin exposure (monitored by flow cytometry using fluorescein isothiocyanate-PAC-1 and phycoerythrin-CD62 antibodies). These responses were markedly amplified by releasates from combined platelet-erythrocyte suspensions. This finding demonstrates a novel mechanism(s) by which erythrocytes intensify platelet aggregability and mediate increased platelet recruitment. Because P-selectin and alpha(IIb)beta(3) are potential sites for platelet-leukocyte interactions, erythrocytes may also modulate leukocyte recruitment. Following aspirin ingestion both the recruiting capacity of platelet releasates and erythrocyte-induced amplification of platelet recruitment were down-regulated. These events represent an additional antithrombotic property of aspirin. We also examined the possibility that arachidonic acid, or eicosanoids derived therefrom, can induce a prothrombotic activity of erythrocytes. The TXA(2)-analog U46 619 and free arachidonate, but not PGI(2) or 12-HETE, induced increases in cytosolic Ca(++) and promoted phosphatidylserine (PS) exposure on a subpopulation of erythrocytes. PS exposure and increases in erythrocyte Ca(++) are associated with enhanced procoagulant activity, increased endothelial adhesion, and reduced erythrocyte deformability. Our findings, therefore, suggest that TXA(2) and arachidonic acid, derived from activated platelets, induce a prothrombotic phenotype on erythrocytes in proximity. We conclude that by these mechanisms, erythrocytes can actively contribute to platelet-driven thrombogenesis and microvascular occlusion.
活化的血小板释放生物活性化合物，进而将更多血小板募集到正在形成的血栓中。我们研究了α（IIb）β（3）的活化以及从胶原处理的血小板获得的释放物所募集的血小板上P-选择素的暴露情况，并评估了血小板-红细胞相互作用和阿司匹林处理对释放物促血栓形成作用的影响。胶原刺激的血小板释放物可诱导α（IIb）β（3）活化和P-选择素暴露（使用异硫氰酸荧光素-PAC-1和藻红蛋白-CD62抗体通过流式细胞术监测）。血小板-红细胞混合悬液的释放物可显著增强这些反应。这一发现揭示了一种新机制，即红细胞可增强血小板聚集能力并介导血小板募集增加。由于P-选择素和α（IIb）β（3）是血小板-白细胞相互作用的潜在位点，红细胞也可能调节白细胞募集。服用阿司匹林后，血小板释放物的募集能力以及红细胞诱导的血小板募集增强作用均下调。这些事件代表了阿司匹林的另一种抗血栓特性。我们还研究了花生四烯酸或其衍生的类二十烷酸是否能诱导红细胞产生促血栓形成活性。TXA（2）类似物U46 619和游离花生四烯酸可诱导红细胞胞质Ca（++）增加，并促进一部分红细胞上磷脂酰丝氨酸（PS）的暴露，但PGI（2）或12-HETE则无此作用。PS暴露和红细胞[Ca（++）]（i）增加与促凝活性增强、内皮黏附增加以及红细胞变形性降低有关。因此，我们的研究结果表明，来自活化血小板的TXA（2）和花生四烯酸可诱导邻近红细胞产生促血栓形成表型。我们得出结论，通过这些机制，红细胞可积极促进血小板驱动的血栓形成和微血管阻塞。
