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

我调查了牛血小板聚集的特征和日本黑牛患Chediak-Higashi综合征（CHS）时胶原诱导血小板聚集减少的病因。牛血小板的特征。与人或大鼠血小板相比，胶原刺激后释放的血栓素A2和ADP对胶原诱导的[Ca^<2+>]_i升高和聚集的贡献较小。蛋白激酶C参与胶原诱导的牛血小板Ca^<2+>信号传导，而这种激酶在人血小板Ca^<2+>信号传导中起聚集作用。胶原蛋白通过激活磷脂酶C在牛血小板中产生肌醇1,4,5 -三磷酸，这是一种Ca^<2+>动员第二信使。胶原蛋白作用于血小板上的两个主要受体；GPIa/IIa和GPVI。对GPVI激动剂惊厥素的反应在CHS血小板中正常，表明GPVI在这些血小板中是正常的。另一方面，对红丝胞素（一种假定的GPIa/IIa激活剂）的反应在CHS血小板中被大大抑制。这表明肌动蛋白聚合参与了胶原蛋白和红丝蛋白产生的Ca^<2+>信号通路。血小板与可溶性胶原的粘附是由GPIa/IIa介导的，在CHS血小板中是正常的。虽然尚不清楚红红菌素是否作用于GPIa/IIa或其他受体，但目前的数据表明，当胶原聚集血小板时，来自红红菌素敏感机制的信号对于GPVI的充分激活是必不可少的。CHS血小板缺乏红红素敏感机制，因此它们有助于澄清胶原受体和受体之间的串扰。

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.