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

胶原蛋白与血小板的相互作用对于止血很重要，尽管胶原蛋白诱导的血小板活化因物种而异，但人们对除人类以外的动物中的血小板聚集机制知之甚少。激动剂反过来增强胶原蛋白的作用。在这项研究中，我们研究了 ADP 和 TXA_2 在胶原蛋白诱导的人、牛和血小板聚集中的作用。胶原蛋白诱导的人血小板聚集高度依赖于TXA_2，而大鼠血小板的聚集依赖于ADP。牛血小板对低剂量的反应。胶原蛋白的产生需要 ADP 和 TXA_2 两者，因为 TXA_2 或 ADP 的作用被阻断，另一种内源性激动剂的作用不出现。当与 ADP 配合时，TXA_2 在胶原诱导的牛血小板聚集中发挥重要作用，然而，牛血小板中胶原蛋白产生的 TXA_2 比人类血小板中的少。牛血小板中的磷酸肌醇 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与人血小板中的不同。 Chediak-Higashi 综合征 (CHS) 显示 ADP 释放量少得多，这可能是由于致密颗粒中 ADP 含量非常稀少。这表明刺激 ADP 释放和生成 TXA_2 的信号在 CHS 血小板中并未受损，尽管该信号。与胶原直接作用的Ca ^ 2+ 动员相关的信号转导系统被大大削弱，因此，在胶原受体的下游，动员内源性激动剂的信号转导系统似乎与胶原的直接作用相关。胶原蛋白是不同的，并且前系统在CHS血小板中没有受损。

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.