Characteristics of aggregation of bovine platelets and clarification of molecular mechanism responsible for a genetic hemorrhagic disease in cattle

我研究了切迪亚克-东氏综合征(CHS)感染的日本黑牛的牛血小板聚集的特征和胶原诱导的血小板聚集减少的病因学。牛血小板的特征。与人或大鼠相比，胶原刺激后释放的血栓素A2和ADP对胶原诱导的牛血小板胞内[Ca~(2+)]_i升高和聚集的贡献较小。蛋白激酶C参与胶原蛋白诱导的牛血小板胞内钙信号转导，而在人血小板中，蛋白激酶C参与聚集而不参与胞外钙信号转导。胶原蛋白通过激活磷脂酶C产生肌醇1，4，5-三磷酸，这是一种动员牛血小板第二信使的钙离子。在CHS中，磷脂酶C的激活受到损害。胶原蛋白作用于血小板上的两个主要受体：GPIa/IIa和GPVI。CHS患者的血小板对GPVI激动剂惊厥毒素的反应正常，表明GPVI在这些血小板中是正常的。另一方面，在CHS的血小板中，对可能的GPIa/IIa激活剂--柔红素的反应被大大抑制。提示肌动蛋白聚合参与了胶原和柔红霉素产生的钙信号转导。CHS患者血小板与可溶性胶原的黏附是正常的，这种黏附是由GPIa/IIa介导的。尽管目前还不能确定红霉素是否作用于GPIa/IIa或其他受体，但目前的数据表明，当胶原蛋白聚集血小板时，来自红霉素敏感机制的信号对于充分激活GPVI是必不可少的。CHS血小板缺乏对红霉素敏感的机制，因此这些机制对于澄清胶原受体和受体之间的串扰是有用的。

I investigated the characteristics of aggregation of bovine platelets and etiology for a decrease in the collagen-induced aggregation of platelets from Japanese Black cattle affected with Chediak-Higashi syndrome (CHS).1. Characteristics of bovine platelets. Contribution of thromboxane A2 and ADP, which are release following stimulation with collagen, to collagen-induced increase in [Ca^<2+>]_i and aggregation in bovine platelets was small compared to human or rat platelets. Protein kinase C was involved in collagen-induced Ca^<2+> signaling in bovine platelets, whereas this kinase plays a role in aggregation rather than in Ca^<2+> signaling in human platelets.2. Collagen produced inositol 1, 4, 5 -trisphosphate, a Ca^<2+> mobilizing second messenger, in bovine platelets through activation of phospholipase C. Activation of phospholipase C was impaired in CHS platelets.3. Collagen acts on two major receptors on platelets ; GPIa/IIa and GPVI. The response to the GPVI agonist convulxin was normal in CHS platelets indicating that GPVI is normal in these platelets. On the other hand, the response to rhodocytin, a putative GPIa/IIa activator, was greatly depressed in CHS platelets. It was suggested that actin polymerization is involved in the collagen- and rhodocytin-produced Ca^<2+> signaling. Adhesion of platelets to soluble collagen, which is mediated by GPIa/IIa, was normal in CHS platelets. Although it remains to be determined whether rhodocytin acts on GPIa/IIa or the other receptor, the present data suggest that a signal from the rhodocytin-sensitive mechanism is indispensable for full activation of GPVI when collagen aggregates platelets. CHS platelets are devoid of the rhodocytin-sensitive mechanism so that these are useful for clarification of collagen receptors and the crosstalk between receptors.