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

胶原蛋白与血小板的相互作用对止血很重要。尽管胶原蛋白诱导的血小板活化因物种不同而不同，但除了人类外，人们对动物体内的血小板聚集机制知之甚少。胶原蛋白从致密颗粒中释放ADP，产生血栓素A2(TXA2)，这些激动剂进而增强胶原蛋白的作用。在本研究中，我们研究了ADP和TXA2在胶原诱导的人、牛和大鼠血小板聚集中的作用，以及参与胶原受体和内源性激动剂作用的信号转导系统。牛血小板对低剂量胶原的反应需要ADP和TXA_2，因为其中一种作用被阻断，另一种内源性激动剂的作用不出现。因此，TXA2在胶原诱导的…聚集中起重要作用。与ADP联合应用时，牛血小板数增加。然而，牛血小板胶原蛋白产生的TXA2比人的少。此外，在牛和人的血小板中，磷脂酰肌醇3-激酶和蛋白激酶C在胶原诱导的释放反应和胶原的直接作用中的作用是不同的。Chediak-Higashi综合征(CHS)牛的血小板释放ADP明显减少，这可能是由于致密颗粒中ADP含量非常少所致。提示CHS血小板刺激ADP释放和产生TXA2的信号并未受到损害，但与胶原直接作用的Ca~(2+)和Gt~(2+)动员有关的信号却明显减弱。因此，在胶原受体下游，动员内源性激动剂的信号转导系统似乎与与胶原直接作用相关的信号转导系统不同，而前者在CHS血小板中没有受到损害。较少

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