Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets.
Binding of annexin V/placental anticoagulant protein I to platelets. Evidence for phosphatidylserine exposure in the procoagulant response of activated platelets.
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DOI：
10.1016/s0021-9258(18)38177-8
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发表时间：
1990-10
期刊：
影响因子：
--
通讯作者：
Perumal Thiagarajan;Jonathan F. Tait
中科院分区：
文献类型：
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作者：
Perumal Thiagarajan;Jonathan F. Tait
膜联蛋白/脂皮质素家族的蛋白在体外通过与阴离子磷脂小泡结合而起到抗凝血剂的作用。在这项研究中，我们研究了膜联蛋白V(胎盘抗凝蛋白I)是否会与人血小板结合。Annexin V以可逆的钙依赖反应与未刺激的血小板结合，其表观解离常数为7 NM，5000-8000个位点/血小板。几种血小板激动剂可诱导更多的结合位点，其作用顺序如下：A23187大于胶原+凝血酶大于胶原大于凝血酶。然而，ADP和肾上腺素都不能诱导额外的结合位点。膜联蛋白家族的另外三种蛋白(膜联蛋白II、膜联蛋白III和膜联蛋白IV)竞争膜联蛋白V与血小板的结合位点，其相对活性与先前观察到的与磷脂小泡结合的相对效价相同。含有磷脂酰丝氨酸的磷脂囊泡可完全抑制膜联蛋白V与血小板的结合。Annexin V可完全阻断125I-FXa与凝血酶刺激的血小板的结合。这些结果支持这一假设，即磷脂酰丝氨酸暴露发生在血小板激活过程中，可能是凝血酶原酶复合体在血小板膜上组装所必需的。
Proteins of the annexin/lipocortin family act as in vitro anticoagulants by binding to anionic phospholipid vesicles. In this study, we investigated whether annexin V (placental anticoagulant protein I) would bind to human platelets. Annexin V bound to unstimulated platelets in a reversible, calcium-dependent reaction with an apparent Kd of 7 nM and 5000-8000 sites/platelet. Additional binding sites could be induced by several platelet agonists in the following order of effectiveness: A23187 greater than collagen + thrombin greater than collagen greater than thrombin. However, neither ADP nor epinephrine induced additional binding sites. Three other proteins of the annexin family (annexins II, III, and IV) competed for annexin V platelets binding sites with the same relative potencies previously observed for binding to phospholipid vesicles. Phospholipid vesicles containing phosphatidylserine completely inhibited binding of annexin V to platelets. Annexin V completely blocked binding of 125I-factor Xa to thrombin-stimulated platelets. These results support the hypothesis that phosphatidylserine exposure occurs during platelet activation and may be necessary for assembly of the prothrombinase complex on platelet membranes.