Research of chemokines and platelet-derived microparticles in progression of thrombotic vascuritis

趋化因子和血小板衍生微粒在血栓性血管炎进展中的研究

• 批准号: 11670718
• 负责人: NOMURA Shosaku
• 金额: $ 2.18万
• 依托单位: Kansai Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670718/
• 关键词: high shear stress; microparticle; cytokine; chemokine; soluble adhesion molecule; diabetes mellitus; arteriosclerosis obliterans; acute myocardial infraction; 急性心筋梗塞症例; 抗血小板療法; P-selectin; PSGL-1; 細胞接着分子; THP-1; 血管内皮細胞

We we used flow cytometry and confocal laser scanning microscopy to investigate the effects of high-shear-induced platelet and microparticle activation in adhesion molecules of THP-1 and endothelial cells (ECs). We also measured the production of some cytokines and studied cytokine mRNA from THP-1 and ECs after PMP stimulation. PMP stimulation of THP-1 cells increased CD11b, CD32, and CD33 but not CD29, CD31, and CD36. PMP stimulation of ECs increased CD54 and CD63 but not CD9, CD29, and CD31. PMPs induced IL-8, IL-1β, and TNFα production by THP-1. PMPs also induced IL-8, IL-1β, and IL-6 production by ECs. Production was time-dependent. With RT-PCR, some cytokine mRNAs were detected in THP-1 and ECs after PMP stimulation. In relation to adhesiveness after PMP stimulation, we could clearly observe a shift in distribution not only of CD11b in THP-1 cells but also of CD54 in ECs.Levels of PMPs and platelet activation markers(Annexin V and CD62P on activated platelets), chemokines(IL-8, monocyte chemotactic peptide 1[MCP-1], and regulated on activation normally T-cell expressed and secreted [RANTES]), and selectins(P-selectin and E-electin)in diabetic patients and healthy control subjects in order to develop a better understanding of their potential contribution to diabetic vascular complications. Significant increases were found for PMPs, P-selectin, MCP-1, RANTES and soluble P- and E-selectins in diabetic individuals, whereas IL-8 levels were similar. These results suggest that high-shear-induced microparticles may contribute to the development of atherosclerosis and participate in vascular damage in inflammatory disorders.

我们利用流式细胞仪和激光共聚焦扫描显微镜研究了高切诱导的血小板和微粒子激活对THP-1和内皮细胞(ECs)黏附分子的影响。我们还检测了PMP刺激后THP-1和ECs产生的一些细胞因子，并研究了细胞因子mRNA的表达。PMP刺激THP-1细胞增加CD11b、CD32和CD33，但不增加CD29、CD31和CD36。PMP刺激内皮细胞可增加CD54和CD63，但不增加CD9、CD29和CD31。PMPs通过THP-1诱导IL-8、IL-1β和肿瘤坏死因子α的产生。PMPs还可诱导内皮细胞产生IL-8、IL-1β和IL-6。生产是依赖时间的。逆转录-聚合酶链式反应检测到PMP刺激后THP-1和ECs中一些细胞因子的mRNAs。在PMP刺激后的黏附方面，我们不仅可以清楚地观察到CD11b在THP-1细胞中的分布，也可以清楚地观察到CD54在ECs中的分布变化。为了更好地了解它们在糖尿病血管并发症中的潜在作用，糖尿病患者和健康对照组中PMPs和血小板激活标志物(活化的血小板上的Annexin V和CD62p)、趋化因子(IL-8、单核细胞趋化肽1[MCP-1]和活化调节T细胞正常表达和分泌[RANTES])以及选择素(P-选择素和E-选择素)的水平发生了变化。糖尿病患者血浆PMPs、P-选择素、MCP-1、RANTES、可溶性P-选择素和E-选择素水平显著升高，而IL-8水平无明显变化。这些结果表明，高切变诱导的微粒可能参与了动脉粥样硬化的发展，并参与了炎性疾病中的血管损伤。

项目成果

Omoto S, Nomura S, Shouzu A, et al.: "Significance of platelet-derived microparticles and activated platelets in diabetic nephropathy"Nephrone. 81. 271-277 (1999)

Omoto S、Nomura S、Shouzu A 等人：“血小板衍生微粒和活化血小板在糖尿病肾病中的意义”Nephrone。

Shosaku Nomura: "Platelet-derived microparticles in patients with arteriosclerosis obliterans : enhancement of high shear-induced microparticle generation by cytokines"Thrombosis Research. 98. 257-268 (2000)

Shosaku Nomura：“动脉硬化闭塞症患者的血小板衍生微粒：细胞因子增强高剪切诱导的微粒生成”血栓形成研究。

Kagawa H, Nomura S, Ozaki Y, et al.: "Effects of nilvadipine-levels and soluble factors in collagen disease complicated with essential hypertension"clinical and Experimental Hypertension. 21. 1177-1188 (1999)

Kakawa H、Nomura S、Ozaki Y 等人：“尼伐地平水平和可溶性因子对胶原病并发原发性高血压的影响”临床和实验性高血压。

Shosaku Nomura: "Platelet-derived microparticles in patients with arteriosclerosis obliterans : enhancement of high shear-induced microparticle generation by cytokines"Throm Res. 98. 257-268 (2000)

Shosaku Nomura：“动脉硬化闭塞症患者中的血小板衍生微粒：细胞因子增强高剪切诱导的微粒生成”Throm Res。

Nomura S, Imamura A, Okuno M, et al.: "Platelet-derived microparticles in patients with arteriosclerosis obliterans: enhancement of high shear-induced microparticles generation by cytokines"Thrombosis Research. (in press).

Nomura S、Imamura A、Okuno M 等人：“动脉硬化闭塞症患者中的血小板衍生微粒：细胞因子增强高剪切诱导的微粒生成”血栓形成研究。