Platelet-microparticles as a carrier of chemical mediators inducing remote organ failure

血小板微粒作为化学介质的载体诱导远端器官衰竭

• 批准号: 12671155
• 负责人: KAWASAKI tomio
• 金额: $ 2.11万
• 依托单位: Osaka 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 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671155/
• 关键词: microparticles; PMN; sepsis; theology; deep vein thrombosis; pulmonary embolism; APCR; 血小板; マイクロパーティクル; 白血球; 化学伝達物質; 接着因子

The chemical mediators are secreted from activated platelets. The mediators actually made a play on peripheral vessels and sometimes made remote organ failure even though those materials are instantaneously resolved in blood. We have identified that the microparticles (MP) released from activated platelets were a transporter of the chemical mediators. In order to clarify the release mechanism and physiological meaning of MP the following projects were performed. MP production, platelet P selectin expression, platelet-monocyte binding, and platelet-polymorphonuclear cell binding increased in number in systemic inflammatory syndrome. Anti-P-selectin antibody clearly inhibited platelets-polymorphonuclear cell aggregation. In addition, leukocyte-platelet interaction and endothelial-MP binding were increased in patients with septic condition. Moreover, when the biorheology of the whole blood from septic patients was analyzed with the microarray bloodstream analyzer, the stiffness of white blood cells was increased. The result indicated that migration of white blood cells through the vessel wall was thought to be impaired. The white blood cells, stiffened by inflammation, may be trapped in the local stasis lesion. The platelet and MP bonded to the white blood cells made a new bonding to the other white blood cells. As a result, quite a new mechanism was advocated that start of coagulation accumulates the chemical mediators in inflammatory lesion. Moreover, it was clarified that the cause of activated protein C resistance (APC-R) in venous thrombosis in our country was not due to factor V Leiden gene mutation as was reported in Europe and America. It is not antibodies to phospholipids but anti-protein S antibodies that express APC-R in Japan. And this is the first report in the world (British Journal of Haematology 2002, 118, 577-583,Thromb Haemost 2002, 88, 716-722).

化学介质由活化的血小板分泌。这些介质实际上在外周血管上发挥作用，有时甚至造成远程器官衰竭，尽管这些物质在血液中会立即分解。我们已经确定，微粒（MP）从活化的血小板释放的化学介质的转运。为了阐明MP的释放机制和生理意义，进行了以下项目。全身性炎症综合征患者MP产生、血小板P选择素表达、血小板-单核细胞结合和血小板-多形核细胞结合数量增加。抗P-选择素抗体明显抑制血小板-多形核细胞聚集。此外，脓毒症患者的白细胞-血小板相互作用和内皮-MP结合增加。此外，当用微阵列血流分析仪分析来自脓毒症患者的全血的生物流变学时，白色血细胞的硬度增加。结果表明，认为白色血细胞通过血管壁的迁移受损。白色血细胞因炎症而变硬，可能被困在局部淤滞病变中。与白色血细胞结合的血小板和MP与其他白色血细胞形成新的结合。因此，提出了一种新的机制，即凝血的启动积累了炎症损伤中的化学介质。阐明了我国静脉血栓形成中活化蛋白C抵抗（APC-R）的原因并非如欧美报道的那样是由于凝血因子V Leiden基因突变所致。在日本，表达APC-R的不是磷脂抗体，而是抗蛋白S抗体。这是世界上第一个报道（British Journal of Haematology 2002，118，577-583，Thromb Haemost 2002，88，716-722）。

项目成果

Ogasawara, N, Kijima, Y., Ike, S., Nakagawa, Y., Takagi, T, Hata, T.Suehisa, E., Kawasaki, T., Miyata, T.: "Hereditary protein S deficiency with a history of recurrent myocardial infarction. -A case report-"Circ. J.. 67・2. 166-168 (2003)

Ogasawara, N, Kijima, Y., Ike, S., Nakakawa, Y., Takagi, T, Hata, T.Suehisa, E., Kawasaki, T., Miyata, T.：“有历史的遗传性蛋白质 S 缺乏症-复发性心肌梗塞的病例报告-“Circ. J. 67・2. 166-168 (2003)

Fujimura H.: "Common C677T polymorphism in the methylenetetrahydrofolate reductase gene increases the risk for deep vein thrombosis in patients with predic position of thrombophilie"Thrombos Res. 98. 1-8 (2000)

Fujimura H.：“亚甲基四氢叶酸还原酶基因中常见的 C677T 多态性会增加具有易栓症预测位置的患者发生深静脉血栓的风险”Thrombos Res。

Nojima J., Kuratsune H, Suehisa E, Kawasaki T., Machii T., Kitani T., Iwatani Y., Kanakura Y.: "Acquired activated protein C resistance associated with anti-protein S antibody as a strong risk factor for DVT in non-SLE patients"Thromb. Haemost.. 88. 716-7

Nojima J.、Kuratsune H、Suehisa E、Kawasaki T.、Machii T.、Kitani T.、Iwatani Y.、Kanakura Y.：“与抗蛋白 S 抗体相关的获得性活化蛋白 C 抵抗是 DVT 的一个强烈危险因素

Suehisa, E., Nomura, T., Kawasaki, T., Kanakura, Y.: "frequency of natural coagulation inhibitor (antithrombin III, Protein C and protein S) deficiencies in Japanese patients with spontaneous deep vein thrombosis."Blood Coagul Fibrinolysis. 12. 95-99 (200

Suehisa, E.、Nomura, T.、Kawasaki, T.、Kanakura, Y.：“日本自发性深静脉血栓形成患者中天然凝血抑制剂（抗凝血酶 III、蛋白 C 和蛋白 S）缺乏的频率。”血液凝固纤溶

Suehisa E., Toku M., Kawasaki T., Kanakura Y.: "Measurement of a newly developed thrombomodulin addition activated partial thromboplastin time assay in patients with deep venous thrombosis"Haemostasis. 31. 26-31 (2001)

Suehisa E.、Toku M.、Kawasaki T.、Kanakura Y.：“深静脉血栓形成患者新开发的血栓调节蛋白添加激活部分凝血活酶时间测定法的测量”止血。