巨噬细胞炎症因子1α对人脑微血管内皮细胞通透性的影响

The Influence of Macrophage Inflammatory Protein-1α(MIP-1α) on Human Brain Microvascular Endothelial Cell Permeability

目的研究巨噬细胞炎症因子1α(MIP-1α)是否具有开通血脑屏障的作用。方法以重组人MIP-1α直接作用于人脑微血管内皮细胞(HBMEC),免疫荧光方法检测紧密连接蛋白ZO-1的分布变化、跨内皮细胞电阻、HRP穿过HBMEC单层的改变、HBMEC细胞CC趋化因子受体5(CCR5)的表达,以及MIP-1α中和抗体和分泌MIP-1α的模式细胞(6T-CEM)与HBMEC单层共同温育时ZO-1的分布变化。结果MIP-1α作用下,HBMEC单层紧密连接结构被破坏,通透性增加,引起HBMEC细胞CCR5受体的表达,MIP-1α中和抗体阻断6T-CEM细胞对HBMEC单层ZO-1分布的改变。结论MIP-1α可能通过CCR5改变HBMEC单层通透性促进T淋巴细胞穿过血脑屏障。

Object To explore whether MIP-1 α has the ability to ＇open＇ blood-brain barrier. Methods Human recommbinant MIP-1 α （rhMIP-1 α ） was incubated with human brain microvascular endothelial cell （HBMEC） monolayer and the permeability of HBMEC monolayer was observed with immunofluorescence, TEER and HRP flux methods. The expression of CC chemokine receptor 5 （CCR5） on HBMECs was assayed with Western blot. Anti-MIP-1 α antibody and 6T-CEM （MIP-1α secreting cell line） were incubated with HBMEC monolayer and the distribution of ZO-1 was observed with immunofluorescence. Results rhMIP-1 α could disrupt tight junction of HBMEC monolayer, anti-MIP-1 α antibody could block the increase of MIP-1 α -induced permeability of HBMEC. rhMIP-1 α could up-regulate the expression of CCR5 in HBMECs. Conclusion MIP-1 a might promote the transendothelial migration of T lymphocytes by interacting with CCR5 in HBMEC monolayer.