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Production and secretion of blood coagulation-fibrinolysis-platelet factors by human monocytes and megakaryocytes.

人单核细胞和巨核细胞产生和分泌凝血-纤溶-血小板因子。

基本信息

批准号：
63480276
负责人：
SATIO Hidehiko
金额：
$ 3.46万
依托单位：
Nagoya University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

Recent studies suggest that leukocytes, platelets and vascular endothelial cells appear to participate actively in the process of thrombosis and hemostasis. We have investigated the production and secretion of blood coagulation-fibrinolysis-platelet factors by two unique human cell lines (MEG-01 and NOMO-1). MEG-01 and NOMO-1 represent good model for human megakaryocytes and monocytes, respectively, When MEG-01 cells were exposed to 10^<-7>M phorbol ester (TPA), they underwent morphological maturation and differentiation, and demonstrated enhanced production of fibrinogen, von Willebrand factor, beta-thromboglobulin, plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2). We have also demonstrated that intracellular ^cAMP-increasing agents enhanced the expression of thrombomodulin (TM) in MEG-01 cells. When MEG-01 cells were exposed to dibutyr _cAMP, forskolin or prostaglandin E_1 TM activity increased 3 15-fold over that of control cells.Northern blot analysis showed time-dependent accumulation of TM mRNA. These results are significant in that it represents the first demonstration of up-regulation of TM. We have also observed similar phenomenon in human vascular endothelial cells. When NOMO-1 cells were exposed to TPA, lipid A or vitamin D3, they secreted increased amounts of interleukin 1, plasminogen activator and plasminogen activator inhibitor. Furthermore, FDP D-dimer was found to stimulate the production and secretion of interleukin 1, suggesting a new link between fibrinolysis and inflamatory reaction.

最近的研究表明，白细胞，血小板和血管内皮细胞似乎积极参与血栓形成和止血的过程。我们研究了两种独特的人类细胞系（MEG-01和NOMO-1）的血液凝固-纤溶-血小板因子的产生和分泌。MEG-01和NOMO-1分别代表了人巨核细胞和单核细胞的良好模型。当MEG-01细胞暴露于10 μ <-7>M佛波醇酯（TPA）时，它们经历形态成熟和分化，并表现出纤维蛋白原、血管性血友病因子、β-血小板球蛋白、纤溶酶原激活物抑制剂1（派-1）和纤溶酶原激活物抑制剂2（派-2）的产生增强。我们还证明了细胞内cAMP增加剂增强了MEG-01细胞中血栓调节蛋白（TM）的表达。二丁酰环腺苷酸（dibutyr _cAMP）处理MEG-01细胞后，Forskolin或PGE_1 TM活性增加3 ~ 15倍，北方印迹分析显示TM mRNA随时间增加而增加。这些结果是重要的，因为它代表了TM上调的第一个证明。我们在人血管内皮细胞中也观察到了类似的现象。当NOMO-1细胞暴露于TPA、脂质A或维生素D3时，它们分泌的白细胞介素1、纤溶酶原激活物和纤溶酶原激活物抑制剂的量增加。FDP D-二聚体刺激白细胞介素1的产生和分泌，提示纤溶与炎症反应之间存在新的联系。