血小板CD40配体对内皮细胞表达组织因子的影响

The Effect of CD40 Ligation in Platelets on the Expression of Tissue Factor in Human Endothelial Cells

目的探讨活化血小板CD40配体对内皮细胞表达组织因子、组织因子抑制物的影响及其分子机制。方法建立活化血小板与人脐静脉内皮细胞的共孵育体系(细胞比例10∶1),观察内皮细胞组织因子及其抑制物表达的变化,以及阻断CD40-CD40配体相互作用对上述效应的影响。结果活化血小板与脐静脉内皮细胞共育8 h后,内皮细胞组织因子mRNA及蛋白表达显著增高,而应用抗CD40配体的抗体和抗CD40抗体可分别抑制其表达(P<0.05)。但是组织因子抑制物mRNA无明显变化。结论活化血小板可通过其表达的CD40配体分子诱导内皮细胞产生组织因子,但并不能增强内皮细胞组织因子抑制物的表达,此效应对不稳定性斑块的形成可能具有促进作用。

Aim To investigate the effects of CD40 ligand from activated platelets on the expression of tissue factor and tissue factor pathway inhibitor in human vascular endothelial ceils （ hUVEC ） and its molecular mechanism. Methods Activated platelets and human umbilical vein endothelial cells were co-incubated in the same systerm, and then the expression of tissue factor and its inhibitor in endothelial cells and the effects of blocking CD40-CD40L signal pathway on their expression were observed. Result After 8 hours of the co-incubation of activated platelets and human umbilical vein endothelial cells, tissue factor mRNA and its protein expression level in hUVEC were raised. Nevertheless these effects could he attenuated by CD40L monoclonal antibody and CIM0 monoclonal antibody added into media before platelets being induced （ P 〈 0.05）, but tissue factor pathway inhibitor mRNA expression level in hUVEC was not changed. Conclusions Activated platelets could induce the expression of tissue factor in endothelial cells by the expression of CIMOL, but could not enhance the expression of tissue factor pathway inhibitor. Tiffs indicates that these effects may play a promoting role in unstable plaque formation and the development of atherosclerosis.