Studies on the signal transduction system of platelet collagen receptor that is related to species difference of hemostasis

胶原-血小板相互作用对止血很重要。虽然胶原诱导的血小板活化因物种而异，但除人类外，对动物血小板聚集的机制知之甚少。胶原蛋白从致密颗粒中释放ADP并产生血栓素A2 (TXA_2)，这些激动剂反过来增强胶原蛋白的作用。本研究探讨了ADP和TXA_2在人、牛和大鼠胶原诱导的血小板聚集中的作用，以及胶原受体联链的信号转导系统和内源性激动剂的作用。胶原诱导的人血小板聚集高度依赖于TXA_2，大鼠血小板聚集依赖于ADP。牛血小板对低剂量胶原的反应需要ADP和TXA_2，因为TXA_2和ADP的作用均被阻断，而另一种内源性激动剂的作用未出现。因此，TXA_2在胶原诱导的牛血小板聚集中发挥了重要作用。然而，胶原蛋白在牛血小板中产生的TXA_2比人血小板少。此外，我们认为磷酸肌肽3激酶和蛋白激酶C在牛血小板中胶原诱导的释放反应和胶原的直接作用中所起的作用与人血小板中不同。患有Chediak-Higashi综合征（CHS）的牛的血小板显示ADP的释放少得多，这可能是由于致密颗粒中ADP含量非常少。提示，CHS血小板刺激ADP释放和生成TXA_2的信号未受损害，但胶原直接作用的Ca^<2+>动员相关信号严重受损。因此，在胶原受体下游，动员内源性激动剂的信号转导系统与直接作用胶原的信号转导系统似乎是不同的，而前者在CHS血小板中没有受损。少

Collagen-platelet interaction is important for hemostasis. Although collagen-induced platelet activation differs depending on species, little is known about the mechanism of platelet aggregation in animals other than humans. Collagen releases ADP from dense granules and generates thromboxane A2 (TXA_2) and these agonists in turn enhance the collagen action. In this study we investigated the roles of ADP and TXA_2 in the collagen-induced aggregation of platelets from humans, cattle and rats and the signal transduction system involved in the linkage of the collagen receptor and the roles of endogenous agonists.Collagen-induced aggregation of human platelets highly depended on TXA_2 and that of rat platelets depended on ADP. The response of bovine platelets to a low dose of collagen required both of ADP and TXA_2 because either of actions of TXA_2 or ADP was blocked the action of the other endogenous agonist did not appear. Thus, TXA_2 plays an important role in the collagen-induced aggre … More gation of bovine platelets when cooperated with ADP. However, the production of TXA_2 due to collagen was less in bovine platelets than in human ones. Furthermore, it is suggested that the roles of phosphoinositide 3-kinase and protein kinase C in the collagen-induced release response and the direct action of collagen are different in bovine platelets from those in human platelets. Platelets from cattle with Chediak-Higashi syndrome(CHS) showed much less release of ADP and this might be due to very scarce ADP content in dense granules. It is suggested that the signal to stimulate ADP release and generate TXA_2 was not impaired in CHS platelets, although the signal related to Ca^<2+> mobilization by the direct action of collagen was greatly impaired. Thus, in the downstream of collagen receptor it seems that the signal transduction system to mobilize endogenous agonists and that related to the direct action of collagen are different and that the former system is not impaired in CHS platelets. Less