Surface expression and functional characterization of α-granule factor V in human platelets:: effects of ionophore A23187, thrombin, collagen, and convulxin
Surface expression and functional characterization of α-granule factor V in human platelets:: effects of ionophore A23187, thrombin, collagen, and convulxin
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DOI：
10.1182/blood.v95.5.1694.005k24_1694_1702
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发表时间：
2000-03-01
期刊：
影响因子：
20.3
通讯作者：
Dale, GL
中科院分区：
文献类型：
--
作者：
Alberio, L;Safa, O;Dale, GL
血小板α颗粒中存在的因子V （FV）在止血中具有重要但尚未完全了解的作用。该报告表明，在凝血酶和惊厥蛋白（一种胶原受体糖蛋白VI的激活剂）两种激动剂同时激活的情况下，一小部分血小板表达非常高水平的表面结合α颗粒FV，这类被激活的血小板亚群占总数的30.7% +/- 4.7%，被称为惊厥蛋白和凝血蛋白诱导的FV （COAT-FV）血小板。在凝血酶和I型、V型或VI型胶原的作用下，也可以观察到COAT-FV血小板的活化，但在iii型胶原的作用下则没有。没有一种单一的激动剂能产生COAT-FV血小板，尽管离子载体A23187与凝血酶或惊血素联合使用时确实能产生这种血小板。COAT-FV血小板与膜联蛋白v结合，表明暴露于氨基磷脂，并在年轻血小板中富集，通过与噻唑橙的结合鉴定。通过证明Xa因子优先结合于COAT-FV血小板，COAT-FV血小板比凝血酶或a23187活化的血小板具有更高的FV活性，以及COAT-FV血小板比任何其他生理激动剂能够产生更多的凝血酶原活性，研究了COAT-FV血小板的功能意义。凝血酶和惊厥素的双重刺激产生的微粒子比A23187少，表明微粒子并不负责观察到的所有活性。这些数据证明了一种新的促凝剂成分产生于凝血酶和胶原蛋白对血小板的双重刺激。COAT-FV血小板可以解释或颗粒FV的独特作用和年轻血小板的止血效果。(C) 2000年由美国血液学会出版。
Factor V (FV) present in platelet alpha-granules has a significant but incompletely understood role in hemostasis. This report demonstrates that a fraction of platelets express very high levels of surface-bound, alpha-granule FV on simultaneous activation with 2 agonists, thrombin and convulxin, an activator of the collagen receptor glycoprotein VI, This subpopulation of activated platelets represents 30.7% +/- 4.7% of the total population and is referred to as convulxin and thrombin-induced-FV (COAT-FV) platelets. COAT-FV platelets are also observed on activation with thrombin plus collagen types I, V, or VI, but not with type iii, No single agonist examined was able to produce COAT-FV platelets, although ionophore A23187 in conjunction with either thrombin or convulxin did generate this population. COAT-FV platelets bound annexin-V, indicating exposure of aminophospholipids and were enriched in young platelets as identified by the binding of thiazole orange. The functional significance of COAT-FV platelets was investigated by demonstrating that factor Xa preferentially bound to COAT-FV platelets, that COAT-FV platelets had more FV activity than either thrombin or A23187-activated platelets, and that COAT-FV platelets were capable of generating more prothrombinase activity than any other physiologic agonist examined. Microparticle production by dual stimulation with thrombin and convulxin was less than that observed with A23187, indicating that microparticles were not responsible for all the activities observed. These data demonstrate a new procoagulant component produced from dual stimulation of platelets with thrombin and collagen. COAT-FV platelets may explain the unique role of or-granule FV and the hemostatic effectiveness of young platelets. (C) 2000 by The American Society of Hematology.