Platelet alpha-granules: basic biology and clinical correlates.
Platelet alpha-granules: basic biology and clinical correlates.
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DOI：
10.1016/j.blre.2009.04.001
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发表时间：
2009-07
期刊：
影响因子：
7.4
通讯作者：
Flaumenhaft R
中科院分区：
文献类型：
--
作者：
Blair P;Flaumenhaft R
α颗粒对正常血小板活性至关重要。这些不寻常的分泌颗粒来源于巨核细胞中受调节的分泌和内吞途径。在小鼠和人类中罕见的α-颗粒形成的遗传缺陷使得能够鉴定介导货物运输和α-颗粒形成的蛋白质。在血小板中，α颗粒在活化时与质膜融合，释放其货物并增加血小板表面积。控制α颗粒膜融合的机制已开始在分子水平上阐明。控制α-颗粒分泌的SNARE和SNARE辅助蛋白已被鉴定。蛋白质组学研究表明，α颗粒释放出数百种生物活性蛋白。蛋白质的这种广度意味着多功能性。虽然最初主要知道它们参与血栓形成和止血，但随着血小板在这些过程的病理生理学中的功能被确定，α颗粒在炎症、动脉粥样硬化、抗微生物宿主防御、伤口愈合、血管生成和恶性肿瘤中的作用已越来越受到重视。本综述将考虑α颗粒的形成，释放和生理作用，特别强调在过去十年中进行的工作。
α–Granules are essential to normal platelet activity. These unusual secretory granules derive their cargo from both regulated secretory and endocytotic pathways in megakaryocytes. Rare, inheritable defects of α–granule formation in mice and man have enabled identification of proteins that mediate cargo trafficking and α–granule formation. In platelets, α–granules fuse with the plasma membrane upon activation, releasing their cargo and increasing platelet surface area. The mechanisms that control α–granule membrane fusion have begun to be elucidated at the molecular level. SNAREs and SNARE accessory proteins that control α–granule secretion have been identified. Proteomic studies demonstrate that hundreds of bioactive proteins are released from α–granules. This breadth of proteins implies a versatile functionality. While initially known primarily for their participation in thrombosis and hemostasis, the role of α–granules in inflammation, atherosclerosis, antimicrobial host defense, wound healing, angiogenesis, and malignancy has become increasingly appreciated as the function of platelets in the pathophysiology of these processes has been defined. This review will consider the formation, release, and physiologic roles of α–granules with special emphasis on work performed over the last decade.
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