Significance of cross-talk among ADP, thromboxane A2 and collagen during collagen-induced thrombus formation

胶原诱导血栓形成过程中 ADP、血栓素 A2 和胶原之间串扰的意义

基本信息

批准号：
17580258
负责人：
ITO Katsuaki
金额：
$ 2.3万
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：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17580258/
关键词：
platelet collagen ADP thromboxane A2 Chediak-Higashi syndrome aggregation bovine 濃染顆粒トロンボキサンA_2

项目摘要

Collagen is the most important platelet activator. It secretes ADP from platelet dense granules and thromboxane A2 (TXA_2) following activation of arachidonic acid cascade. ADP and TXA_2 in turn potentiate the action of collagen. However, detailed mechanism for synergism among collagen, ADP and TXA_2 is not fully elucidated. In this study, we investigated the synergism produced by these activators using bovine and rat platelets. Main findings are as follows.1) U46619, an active analog of TXA_2, did not cause aggregation by itself, but when combined with ADP at a sub threshold concentration, they caused considerable aggregation. Combination of ADP and U46619 synergistically elevated [Ca^<2+>]i. ADP P2Y1 receptor rather than P2Y12 receptor was though to be involved in the increase in [Ca^<2+>]i and aggregation produced 3y combination of ADP and U46619.2) Collagen and ADP also potentiated the aggregation. Activation of integrin a2pi, one of collagen receptor, by ADP may be responsible for the potentiation.3) No synergism was observed between U46619 (TXA_2) and collagen.4) In platelets from cattle or rats with Chediak-Higashi syndrome (CHS), dense granules are poorly developed, thereby ADP secretion was extremely inhibited in these platelets. Decreased secretion of ADP leads to impaired crosstalk between ADP or TXA_2 and that between ADP and collagen, resulting in decreased aggregation response, However, P-selectin release from a-granules was normal in platelets form cattle and rats with CHS.In human platelets it has been reported that ADP synergizes with TXA_2 through P2Y12 receptor, i.e. probably the PI3 kinase - Akt pathway is involved. In contrast, our data suggest that synergism between ADP and TXA_2 is mainly mediated through P2Y1 receptor in bovine platelets. Ca^<2+> may be important for the synergism. Thus, it seems that the mechanism involved in the crosstalk between platelet agonists is different depending on animal species.

胶原蛋白是最重要的血小板激活剂。在花生四烯酸级联激活后，它从血小板致密颗粒和血栓素 A2 (TXA_2) 中分泌 ADP。 ADP 和 TXA_2 反过来会增强胶原蛋白的作用。然而，胶原蛋白、ADP和TXA_2之间协同作用的详细机制尚未完全阐明。在这项研究中，我们使用牛和大鼠血小板研究了这些激活剂产生的协同作用。主要研究结果如下：1)U46619是TXA_2的活性类似物，其本身不会引起聚集，但当与亚阈值浓度的ADP结合时，它们引起相当大的聚集。 ADP和U46619的组合协同升高[Ca 2+ ]i。 ADP P2Y1 受体而不是P2Y12 受体被认为参与[Ca 2+ ]i 的增加并且聚集产生ADP和U46619.2)的3y组合。胶原和ADP也增强了聚集。 ADP 激活整合素 a2pi（胶原蛋白受体之一）可能是增强作用的原因。3) U46619 (TXA_2) 和胶原蛋白之间没有观察到协同作用。4) 在来自患有 Chediak-Higashi 综合征 (CHS) 的牛或大鼠的血小板中，致密颗粒发育不良，因此这些血小板中ADP的分泌受到极大抑制。 ADP 分泌减少导致 ADP 或 TXA_2 之间以及 ADP 和胶原蛋白之间的串扰受损，从而导致聚集反应降低。然而，在患有 CHS 的牛和大鼠血小板中，α-颗粒中的 P-选择素释放是正常的。有报道称ADP通过P2Y12受体与TXA_2产生协同作用，即可能涉及PI3激酶-Akt通路。相反，我们的数据表明 ADP 和 TXA_2 之间的协同作用主要通过牛血小板中的 P2Y1 受体介导。 Ca 2+ 对于协同作用可能很重要。因此，似乎血小板激动剂之间的串扰所涉及的机制因动物种类而异。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Alteration of release and roles of ADP and thromboxane A_2 during collagen-induced aggregation of platelets from cattle with Chediak-Higashi syndrome

Chediak-Higashi 综合征牛胶原诱导血小板聚集过程中 ADP 和血栓素 A_2 的释放和作用的改变

DOI：
发表时间：
2007
期刊：
Am. J. Vet. Res. (in press)
影响因子：
0
作者：
Honda N;Ohnishi K;Fujishiro T;Ikeda M;Ito K
通讯作者：
Ito K

Chediak-Higashi症候群における血小板凝集異常

Chediak-Higashi 综合征中的血小板聚集异常

DOI：
发表时间：
2007
期刊：
血液フロンティア 17 (4)
影响因子：
0
作者：
Horiuchi;T.;伊藤勝昭
通讯作者：
伊藤勝昭

Platelet dysfunction accompanied with Chediak-Higashi syndrome (in Japanese, review)

伴有 Chediak-Higashi 综合征的血小板功能障碍（日语，综述）

DOI：
发表时间：
2007
期刊：
Hematology Frontier (Ketsueki Frontier) 17 (4)
影响因子：
0
作者：
K.M.Ito;M.Okayasu;C.Koshimoto;A.Shinohara;Y.Asada;K.Tsuchiya T.Sakamoto;K.Ito.;Ito K.
通讯作者：
Ito K.

Impairment of endothelium-dependent relaxation of aortas and pulmonary arteries from spontaneously hyperlipidemic mice (Apodemus sylvaticus)