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MOLECULAR CELL BIOLOGICAL STUDIES ON EXPRESSION MECHANISM OF TISSUE FACTOR IN ENDOTHELIAL CELLS.

内皮细胞组织因子表达机制的分子细胞生物学研究。

基本信息

批准号：
07672355
负责人：
NAKAMURA Shin
金额：
$ 1.47万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07672355/
关键词：
Endothelial Cells Monocytes Neutrophils Tissue Factor Thrombosis Atherosclersis 動脈硬化顆粒球 Fissue Factor 血栓症抗PAF剤 Tissue Factor 血液凝固

项目摘要

Tissue factor (thromboplastin, factor III) is a receptor-like membrane protein expressed on cell surface to initiate blood coaqulation cascade reaction through binding with plasma factor VII/VIIa. Tissue factor is known tobe expressed in endothelial cells, neutrophils and/or monocytes only upon their stimulation with LPS,cytokines, stress, PAF,and other inflammatory mediators. Hyperexpression of tissue factor of these cells directly causes abnormal hypercoagulopathy including thrombosis in brain and/or heart.In this project We investigate expression mechanism and fucntion of tissue factor in endothelial cells, neutrophils and/or monocytes on molecular cell biological bases. We also studied on in vivo mechanism of tissue factor-mediated intravascular coagulation or thrombosis. Followings are research results in this project.1.Research techniques of sandwich ELISA,flow-cytometry, immunohistochmical stain, RT-PCR were established to investigate expression mechanism of tissue factor on molecular cell biological bases.2.The expression and clearance mechanisms (vesicle shedding and endocytosis) of tissue factor in LPS-stimulated human endothelial cells were studied.3.A regulation mechanism by shear stress to cytokine-mediated tissue factor expression by human endothelial cells was deduced on gene transcriptional level.4.A new neutrophil function to express tissue factor was found. This neutrophil tissue factor expression was mediated by an interaction between endothelial cells and leukocytes and suggested to be a possible causes of intravascular coagulation or thrombosis by in vivo studies.5.Another new finding was signal transducing function of tissue factor in monocytes. This function was triggered by binding with factor VII/VIIa on cell surface and mediated by tissue factor associated gamma-chain.

组织因子(凝血活酶，因子III)是一种表达于细胞表面的受体样膜蛋白，通过与血浆凝血因子VII/VIIa结合启动凝血级联反应。已知组织因子仅在内皮细胞、中性粒细胞和/或单核细胞在内毒素、细胞因子、应激、PAF和其他炎症介质刺激下表达。这些细胞的组织因子的高表达直接导致异常的高凝状态，包括脑和/或心脏的血栓形成。本课题从分子细胞生物学的角度研究组织因子在血管内皮细胞、中性粒细胞和/或单核细胞中的表达机制和功能。我们还对组织因子介导的血管内凝血或血栓形成的体内机制进行了研究。本课题的研究成果如下：1.建立了夹心ELISA法、流式细胞术、免疫组织化学染色、RT-PCR等研究技术，从分子细胞生物学基础上探讨了组织因子的表达机制。2.研究了组织因子在脂多糖刺激的人内皮细胞中的表达和清除机制(囊泡脱落和内吞作用)。3.在基因转录水平上推测了剪切力对人内皮细胞细胞因子介导的组织因子表达的调节机制。4.发现了一种新的中性粒细胞表达组织因子的功能。这种中性粒细胞组织因子的表达是由内皮细胞和白细胞之间的相互作用介导的，体内研究表明这可能是血管内凝血或血栓形成的原因之一。5.单核细胞中组织因子的信号转导功能是另一个新发现。这一功能是通过与细胞表面的因子VII/VIIa结合而触发的，并由组织因子相关的伽马链介导。