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

与止血种属差异相关的血小板胶原受体信号转导系统的研究

• 批准号: 15580261
• 负责人: ITO Katsuaki
• 金额: $ 2.43万
• 依托单位: University of Miyazaki
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15580261/
• 关键词: collagen; species difference; ADP; thromboxane A2; platelet aggregation; synergism; signal transduction system; Chediak-Higashi syndrome; 凝集; Chedaik-Higashi症候群; 血小板

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

胶原蛋白血小板相互作用对于止血很重要。尽管胶原蛋白诱导的血小板激活取决于物种的不同，但对人类以外的动物的血小板聚集机理知之甚少。胶原蛋白从致密颗粒中释放出ADP，并生成血栓烷A2（TXA_2），这些激动剂又增强了胶原蛋白的作用。在这项研究中，我们调查了ADP和TXA_2在人类，牛和大鼠胶原蛋白诱导的血小板聚集中的作用，以及与内源性激动剂的胶原蛋白受体链接的信号转导系统有关。胶原蛋白引起的人血小板在TXA_2和call dect the and depant and depant and and depant and the and destpaleT and dect and callect and dect and decation。牛血小板对低剂量的胶原蛋白的响应都需要ADP和TXA_2的响应，因为TXA_2或ADP的任何动作都无法阻止其他内源性激动剂的作用。这是TXA_2在胶原蛋白引起的Acn中发挥重要作用……与ADP合作时，更多的牛血小板。然而，牛血小板中由于胶原蛋白引起的TXA_2的产生比人类血小板少。此外，有人提出，磷酸肌醇3-激酶和蛋白激酶C在胶原蛋白诱导的释放反应中的作用，而牛血小板中胶原蛋白的直接作用与人血小板中的作用不同。牛的血小板患有Chediak-Higashi综合征（CHS）显示出ADP的释放少得多，这可能是由于密集颗粒中的ADP含量非常稀少。建议在CHS血小板中刺激ADP释放和生成TXA_2的信号并没有受到损害，尽管通过胶原蛋白的直接作用与CA^<2+>动员有关的信号非常受损。在胶原受体的下游中，似乎动员内源性激动剂的信号转导系统与胶原蛋白的直接作用有关，而前者在CHS血小板中不会受到损害。较少的

项目成果

A new monoclonal antibody, mAb 204-11, that influences the binding of platelet GPVI to fibrous collagen

一种新型单克隆抗体 mAb 204-11，可影响血小板 GPVI 与纤维胶原的结合

• 发表时间: 2003
• 期刊: Thrombosis Haemostasis 89(6)
• 作者: Moroi;M.;Mizuguchi;J.;Kawashima;S.;Nagamatsu;M.;Miura;Y.;Nakagaki;T.;Ito;K;Jung;S.M.
• 通讯作者: S.M.

Moroi, M., Mizuguchi, J., Kawashima, S., Nagamatsu, M., Miura, Y., Nakagaki, T., Ito, K., Jung, S.M.: "A new monoclonal antibody, mAb 204-11, that influences the binding of platelet GPVI to fibrous collagen"Thrombosis Haemostasis. 89(6). 996-1003 (2003)

Moroi, M.、Mizuguchi, J.、Kawashima, S.、Nagamatsu, M.、Miura, Y.、Nakagaki, T.、Ito, K.、Jung, S.M.：“一种新的单克隆抗体，mAb 204-11，

Inhibition of protein kinase C-mediated contraction by Rho kinase inhibitor fasudil in rabbit aorta

• DOI: 10.1007/s00210-004-0975-9
• 发表时间: 2004-10
• 期刊: Naunyn-Schmiedeberg's Archives of Pharmacology
• 作者: Erika Shimomura;M. Shiraishi;T. Iwanaga;M. Seto;Y. Sasaki;M. Ikeda;Katsuaki Ito

A new monoclonal antibody, mAb 204-11, that influence the binding of platelet GPVI to fibrous collagen

一种新型单克隆抗体 mAb 204-11，可影响血小板 GPVI 与纤维胶原的结合

• 发表时间: 2003
• 期刊: Thrombosis Haemostasis 89(6)
• 作者: Moroi;M.;Mizuguchi;J.;Kawashima;S.;Ito;K.;Jung;S.M.et al.
• 通讯作者: S.M.et al.

Essential role of Rho kinase in Ca^<2+> sensitization of prostaglandin F2α-induced contraction of rabbit aortae.

Rho激酶在前列腺素F2α诱导的兔主动脉收缩的Ca ^ 2+ 敏化中的重要作用。

• 发表时间: 2003
• 期刊: J.Physiol.(Lond.) 546(3)
• 作者: Ito;K.;Shimomura;E.;Iwanaga;T.;Shiraishi;M.;Shindo;K.;Nakamura;J.;Nagumo;H.;Seto;M.;Sasaki;Y.;Takuwa;Y.
• 通讯作者: Y.