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

最近的研究表明，白细胞、血小板和血管内皮细胞积极参与血栓形成和止血过程。我们研究了两种独特的人类细胞系（MEG-01和NOMO-1）的凝血-纤溶-血小板因子的产生和分泌。MEG-01和NOMO-1分别代表了人类巨核细胞和单核细胞的良好模型，当MEG-01细胞暴露于10^<-7>M phorbol酯（TPA）时，它们经历了形态成熟和分化，并表现出纤维蛋白原、血管性血液病因子、β -血栓球蛋白、纤溶酶原激活物抑制剂1 （PAI-1）和纤溶酶原激活物抑制剂2 （PAI-2）的增强。我们还证明了细胞内的camp增加剂增强了MEG-01细胞中血栓调节素（TM）的表达。当MEG-01细胞暴露于dibutyr _cAMP时，forskolin或前列腺素E_1 TM的活性比对照细胞增加了3 - 15倍。Northern blot分析显示TM mRNA的积累具有时间依赖性。这些结果具有重要意义，因为它首次证明了TM的上调。我们在人血管内皮细胞中也观察到类似的现象。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、纤溶酶原激活剂和纤溶酶原激活剂抑制剂的数量增加。此外，FDP -二聚体被发现可以刺激白细胞介素1的产生和分泌，这表明纤溶和炎症反应之间存在新的联系。

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.