Intracellular origin and ultrastructure of platelet-derived microparticles.

Intracellular origin and ultrastructure of platelet-derived microparticles.
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DOI:
10.1111/jth.13745
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发表时间:
2017-08
期刊:
Journal of thrombosis and haemostasis : JTH
影响因子:
--
通讯作者:
Weisel JW
Weisel JW
中科院分区:
其他
文献类型:
--
作者:
Ponomareva AA;Nevzorova TA;Mordakhanova ER;Andrianova IA;Rauova L;Litvinov RI;Weisel JW

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血小板衍生的微粒构成了循环血液微粒的主要群体,这些微粒在止血和血栓形成中发挥着重要作用。尽管对血小板衍生微粒的(病理)生理作用进行了大量的研究,但它们的形成机制和结构细节仍然很大程度上是未知的。在这里,我们研究了来自分离的人血小板的血小板衍生微粒的形成、超微结构和组成,无论是静止的还是由下列激活剂之一刺激的:花生四烯酸、ADP、胶原、凝血酶或钙离子载体A23187。用流式细胞仪、透射和扫描电子显微镜分析了血小板释放的亚细胞颗粒的细胞内来源、结构多样性和大小分布。微粒的结构、尺寸和细胞内来源取决于激活细胞的刺激。主要结构群包括一个被一个薄膜或多个囊泡结构包围的小泡。与其他刺激不同的是,凝血酶不仅能从血小板质膜上诱导微粒的形成,还能从细胞内的结构中诱导微粒的形成。其中一部分来源于细胞内的囊泡颗粒含有细胞器,如线粒体、糖原颗粒和空泡。血小板衍生微粒的大小取决于细胞激活刺激的性质。这些结果为不同类型的血小板激活剂的性质差异、MPS的特殊生理和病理效应以及先进检测方法的发展提供了结构基础。
Platelet-derived microparticles comprise the major population of circulating blood microparticles that play an important role in hemostasis and thrombosis. Despite numerous studies on the (patho)physiological roles of platelet-derived microparticles, mechanisms of their formation and structural details remain largely unknown. Here we studied the formation, ultrastructure, and composition of platelet-derived microparticles from isolated human platelets, either quiescent or stimulated with one of the following activators: arachidonic acid, ADP, collagen, thrombin, or calcium ionophore A23187. Using flow cytometry, transmission and scanning electron microscopy, we analyzed the intracellular origin, structural diversity, and size distributions of the subcellular particles released from platelets. The structure, dimensions, and intracellular origin of microparticles depend on the cell-activating stimulus. The main structural groups include a vesicle surrounded by one thin membrane or multivesicular structures. Thrombin, unlike other stimuli, induced formation of microparticles not only from the platelet plasma membrane but also from intracellular structures. A fraction of these vesicular particles having an intracellular origin contained organelles, such as mitochondria, glycogen granules, and vacuoles. The size of platelet-derived microparticles depended on the nature of the cell-activating stimulus. The results obtained provide a structural basis for the qualitative differences of various platelet activators, for specific physiological and pathological effects of MPs, and for development of advanced assays.
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