Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets
Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets
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DOI：
10.1096/fj.02-0574fje
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发表时间：
2003-01-01
期刊：
影响因子：
4.8
通讯作者：
Engelmann, B
中科院分区：
文献类型：
--
作者：
Müller, I;Klocke, A;Engelmann, B
组织因子是生理性凝血和病理性血栓形成的主要起始物，虽然最近被证实存在于人的血液中，但血管内因子的功能意义和位置尚不清楚。在血液的血浆部分，我们发现Tf主要与循环中的微泡有关。通过特异性标记CD42b的细胞分选，血小板来源的微泡被确认为血浆转铁蛋白的主要位置。激活的血小板急剧脱落的微泡中存在全长转铁蛋白，证实了这一点。结果表明，静息状态下的血小板α颗粒和开放的小管系统中均有TF的储存，活化后暴露于细胞表面。通过P-选择素和中性粒细胞受体(PSGL-1，CD18整合素)的相互作用，当微囊和血小板与中性粒细胞黏附时，血基转移因子的功能被激活。此外，中性粒细胞分泌的氧自由基支持血管内转铁蛋白的活性。血小板池和微泡转铁蛋白对全血转铁蛋白活性的贡献是相加的，且程度相当，这表明微泡转铁蛋白的大量参与。我们的结果引入了一个新的概念，即转铁蛋白介导的凝血主要依赖于与微泡和激活的血小板相关的转铁蛋白，这主要使整个凝血系统能够在受限的细胞表面进行。
Although tissue factor (TF), the principial initiator of physiological coagulation and pathological thrombosis, has recently been proposed to be present in human blood, the functional significance and location of the intravascular TF is unknown. In the plasma portion of blood, we found TF to be mainly associated with circulating microvesicles. By cell sorting with the specific marker CD42b, platelet-derived microvesicles were identified as a major location of the plasma TF. This was confirmed by the presence of full-length TF in microvesicles acutely shedded from the activated platelets. TF was observed to be stored in the alpha-granules and the open canalicular system of resting platelets and to be exposed on the cell surface after platelet activation. Functional competence of the blood-based TF was enabled when the microvesicles and platelets adhered to neutrophils, as mediated by P-selectin and neutrophil counterreceptor (PSGL-1, CD18 integrins) interactions. Moreover, neutrophil-secreted oxygen radical species supported the intravascular TF activity. The pools of platelet and microvesicle TF contributed additively and to a comparable extent to the overall blood TF activity, indicating a substantial participation of the microvesicle TF. Our results introduce a new concept of TF-mediated coagulation crucially dependent on TF associated with microvesicles and activated platelets, which principally enables the entire coagulation system to proceed on a restricted cell surface.