Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype
Glycoprotein V-deficient platelets have undiminished thrombin responsiveness and do not exhibit a Bernard-Soulier phenotype
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DOI：
10.1182/blood.v94.12.4112.424k40_4112_4121
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发表时间：
1999-12-15
期刊：
影响因子：
20.3
通讯作者：
Coughlin, S
中科院分区：
文献类型：
--
作者：
Kahn, ML;Diacovo, TG;Coughlin, S
血小板通过血管性血友病因子（vWF）粘附到细胞外基质和凝血酶激活血小板是止血的关键步骤。糖蛋白（GP）V是GPIb-V-IX复合物（vWF的血小板受体）的组分。GPV也被凝血酶裂解。GPIb或GPIX缺乏导致Bernard-Soulier综合征（BSS），这是一种出血性疾病，其中血小板巨大且具有多种功能缺陷。GPV缺乏是否也可能导致BSS尚不清楚，GPV在血小板-vWF相互作用和凝血酶信号传导中的作用也是未知的。我们报告说，与野生型小鼠相比，GPV缺陷小鼠发育正常，没有自发出血的证据，尾部出血时间也没有延长。通过流式细胞术和电子显微镜评估，GPV缺陷型血小板的大小和结构正常。GPV缺陷型和野生型血小板在Botrocetin介导的血小板凝集和它们粘附于小鼠vWF Al结构域的能力方面是不可区分的。与野生型相比，GPV缺陷型血小板对低浓度和高浓度凝血酶的血小板聚集和ATP分泌没有减少。我们的研究结果表明：（1）GPV不是血小板中GPIb表达和功能所必需的，GPV缺乏不太可能是人类BSS的原因;（2）GPV不是强大的凝血酶信号传导所必需的。是否冗余占缺乏表型的GPV缺陷或GPV是否提供微妙的或尚未探测的功能，在血小板或其他细胞仍有待确定。(C)1999年，美国血液学会。
Adhesion of platelets to extracellular matrix via von Willebrand factor (vWF) and activation of platelets by thrombin are critical steps in hemostasis. Glycoprotein (GP) V is a component of the GPIb-V-IX complex, the platelet receptor for vWF. GPV is also cleaved by thrombin. Deficiency of GPIb or GPIX results in Bernard-Soulier syndrome (BSS), a bleeding disorder in which platelets are giant and have multiple functional defects. Whether GPV-deficiency might also cause BSS is unknown as are the roles of GPV in platelet-vWF interaction and thrombin signaling. We report that GPV-deficient mice developed normally, had no evidence of spontaneous bleeding, and had tail bleeding times that were not prolonged compared with wild-type mice. GPV-deficient platelets were normal in size and structure as assessed by flow cytometry and electron microscopy. GPV-deficient and wild-type platelets were indistinguishable in botrocetin-mediated platelet agglutination and in their ability to adhere to mouse vWF Al domain. Platelet aggregation and ATP secretion in response to low and high concentrations of thrombin were not decreased in GPV-deficient platelets compared with wild-type. Our results show that (1) GPV is not necessary for GPIb expression and function in platelets and that GPV deficiency is not likely to be a cause of human BSS and (2) GPV is not necessary for robust thrombin signaling. Whether redundancy accounts for the lack of phenotype of GPV-deficiency or whether GPV serves subtle or as yet unprobed functions in platelets or other cells remains to be determined. (C) 1999 by The American Society of Hematology.