Adenosine diphosphate induces binding of von Willebrand factor to human platelets.
Adenosine diphosphate induces binding of von Willebrand factor to human platelets.
复制标题
二磷酸腺苷诱导冯维勒布兰德因子与人血小板的结合。
作者：
Fujimoto,T;Hawiger,J
血小板通过其激活、粘附到血管损伤区域和聚集的机制来封闭血管壁的渗漏，以防止出血1。这种生理上重要的止血过程需要因子 VIII/血管性血友病因子 (vWF)，这是一种在称为血管性血友病的遗传性出血性疾病中缺失的血浆糖蛋白，在这种疾病中，血小板无法粘附到血管壁的内皮下层2。因此，vWF 对于将血小板锚定在血管壁上是必要的，并且它介导血小板与血小板的相互作用。这种相互作用需要血小板表面有适当的受体。直到最近，抗生素瑞斯托菌素还被用来诱导体外受体介导的 vWF 与血小板的结合，并引起其聚集或凝集 3-7。尽管瑞斯托菌素是一种有用的实验室工具，但它显然是非生理性的，因此我们将注意力转向了凝血酶，它在静脉穿刺后 45 秒内出现在静脉血中，是一种非常有效的血小板聚集生理诱导剂。凝血酶使血小板形状从盘状改变为多刺球体，并改变血小板膜，导致 ADP、血清素和血小板储存颗粒的其他成分释放。我们最近发现，血液中的低浓度（0.1-0.5 nM）凝血酶可诱导 vWF 与特定血小板受体结合10。我们现在报道，ADP 添加到血小板中也会诱导 vWF 与血小板受体的结合。此外，由凝血酶从血小板储存颗粒释放的ADP至少部分地负责随后125 I标记的vWF的结合。
Blood platelets seal off leaks in the vessel wall to prevent haemorrhage by a mechanism involving their activation, adhesion to the zone of vessel injury and aggregation1. This physiologically important haemostatic process requires Factor VIII/von Willebrand factor (vWF), a plasma glycoprotein missing in the genetic, haemorrhagic disorder called von Willebrand disease, in which platelets cannot adhere to the subendothelial layer of the vessel wall2. Thus vWF is necessary for anchoring platelets to the vessel wall, and it mediates platelet–platelet interaction. This interaction requires an appropriate receptor on the platelet surface. Until recently, the antibiotic ristocetin was used to inducein vitroreceptor-mediated binding of vWF to platelets and to cause their aggregation or agglutination3–7. But although a useful laboratory tool8, ristocetin is clearly non-physiological, so we turned our attention to thrombin, which appears in venous blood within 45 s of venipuncture and is a very potent physiological inducer of platelet aggregation. Thrombin causes platelets to change shape from discoid to spiny spheres, and alters the platelet membrane resulting in release of ADP, serotonin and other constituents of platelet storage granules9. We recently showed that low concentrations (0.1–0.5 nM) of thrombin, attainable in blood, induce binding of vWF to a specific platelet receptor10. We now report that the binding of vWF to platelet receptors is also induced by ADP on its addition to platelets. Moreover, ADP released from platelet storage granules by thrombin is, at least in part, responsible for subsequent binding of125I-labelled vWF.