多形核白细胞导致血管内皮细胞粘附蛋白磷酸化和通透性增高  

Polymorphonuclears induce phosphorylation of adherens junction proteins and hyperpermeability in capillary vascular endothelial cells

作　　者：马维亚[1] 王发强[1] 徐波[1] 纪惠茹[1] 

机构地区：[1]武警总医院神经内科,北京100039

出　　处：《武警医学》2002年第3期142-146,共5页Medical Journal of the Chinese People's Armed Police Force

摘　　要：目的　内皮细胞粘附连接 (AJ)是由交换膜粘附蛋白复合物构成的。其中 β -catenin将血管内皮细胞VE -cad herin与细胞骨架蛋白连接在一起 ,并在其相互调节中起信号作用。本研究致力于激活的多形核白细胞 (PMNs)对血管内皮细胞完整性和β -catenin和VE -cadherin的修饰作用。 方法　本文采用免疫沉淀、Western印迹法和双室式单层细胞模型系统检测白蛋白通过内皮细胞的清除率。结果　测得激活的PMNs可导致 β -catenin和VE -cadherin酪氨酸磷酸化表达增加和培养的单层内皮细胞通透性增高 ;而抑制 β -catenin和VE -cadherin可以封闭内皮细胞的高通透性反应。结论　本研究首次将激活的PMNs引起AJ蛋白磷酸化与导致培养的微血管内皮细胞通透性增高结合起来 ,提示激活的PMNs可通过 β -catenin和VE-cadherin使内皮细胞构型改变来调节内皮屏障功能。Objective The endothelial adherens junction(AJ) is formed by complexes of transmembrane adhesive proteins,of which β-catenin connects the junctional protein vascular endothelial(VE)-cadherin to the cytoskeleton and plays a signaling role in the regulation of junction-cytoskeleton interaction.In this study,we investigated the effect of neutrophil activation on endothelial monolayer integrity and on β-catenin and VE-cadherin modification.Methods Immunoprecipitation,Western blot analysis and albumin clearance across the monolayer were used.Results Activated neutrophils induced a significant increase in tyrosine phosphorylation of β-catenin and VE-cadherin and an elevated permeability of capillary vascular endothelial cells.And inhibition of phosphorylation of β-catenin and VE-cadherin blocked the hyperpermeability response in the endothelial cells.Conclusions Our results are the first to link neutrophil-mediated changes in phosphorylation of AJ proteins with hyperpermeability in microvascular endothelial cells.These data suggest that neutrophils may regulate endothelial barrier function through a process conferring conformational changes to β-catenin and VE-cadherin.

关 键 词：多形核白细胞 血管内皮细胞 β-catenin VE-CADHERIN 酪氨酸磷酸化 通透性 

分 类 号：R543[医药卫生—心血管疾病]