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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。它通过激活花生四烯酸级联反应，从血小板致密颗粒中分泌ADP和血栓素A_2（TXA_2）。ADP和TXA_2又加强胶原的作用。然而，胶原、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，我们研究了这些激活剂使用牛和大鼠血小板产生的协同作用。主要结果如下：1）TXA_2活性类似物U46619本身不引起聚集，但与阈下浓度的ADP联合作用时，可引起明显的聚集。ADP和U46619联合使用可协同升高[Ca^<2+>]i。ADP与U46619联合作用引起的[Ca^（2+）]i升高和聚集可能与ADP P2 Y1受体有关，而与P2 Y12受体无关。U46619（TXA_2）与胶原之间无协同作用。4）Chediak-Higashi综合征（CHS）牛和大鼠血小板致密颗粒发育不良，ADP分泌受到严重抑制。ADP分泌减少，ADP或TXA_2之间以及ADP与胶原之间的相互作用减弱，导致血小板聚集反应降低，而牛和大鼠CHS血小板α颗粒P-选择素释放正常，人血小板中ADP与TXA_2的协同作用可能通过P2 Y12受体，即PI 3激酶- Akt途径。ADP与TXA_2的协同作用主要是通过牛血小板P2 Y1受体介导的。Ca^<2+>可能是协同作用的重要因素。因此，似乎血小板激动剂之间的串扰所涉及的机制取决于动物物种而不同。

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)