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

牛血小板聚集特征及牛遗传性出血病分子机制的阐明

基本信息

批准号：
12660272
负责人：
ITO Katsuaki
金额：
$ 2.24万
依托单位：
Miyazaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

项目摘要

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.

我调查了牛血小板聚集的特征和日本黑牛感染Chediak-Higashi综合征（CHS）的胶原诱导的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对胶原诱导的牛血小板[Ca^2+]_i增加和聚集的贡献很小。蛋白激酶C在牛血小板中参与胶原诱导的Ca^<2+>信号传导，而在人血小板中该激酶在聚集中起作用而不是Ca^<2+>信号传导.胶原蛋白通过激活磷脂酶C在牛血小板中产生1，4，5 -三磷酸肌醇（Ca^<2+>动员第二信使）。CHS血小板中磷脂酶C的活化受损.胶原蛋白作用于血小板上的两种主要受体; GPIa/IIa和GPVI。对GPVI激动剂惊厥素的反应在CHS血小板中是正常的，表明GPVI在这些血小板中是正常的。另一方面，红细胞素，一个假定的GPIa/IIa激活剂的反应，在CHS血小板大大压抑。这表明肌动蛋白聚合参与了胶原蛋白和红细胞素产生的Ca^2+信号传导。血小板与可溶性胶原的粘附在CHS血小板中是正常的，其由GPIa/IIa介导。尽管红细胞素是否作用于GPIa/IIa或其他受体仍有待确定，但目前的数据表明，当胶原蛋白聚集血小板时，来自红细胞素敏感机制的信号对于GPVI的完全激活是必不可少的。CHS血小板缺乏红细胞素敏感机制，因此这些血小板可用于澄清胶原受体和受体之间的串扰。