阿尔茨海默病人外周血T细胞穿过血脑屏障入脑需要其过表达的MIP-1α与脑内皮细胞上CCR5受体的相互作用(英文)

【作者】 陈誉华； 曼淑梅； 马怡然； 尚德淑； 郭大文； 赵伟东； 李波； 方文刚； 朱莉；

【机构】 中国医科大学发育生物学教研室卫生部细胞生物学重点实验室；

【摘要】 <正>Peripheral T lymphocytes in Alzheimer’s disease overexpress MEP-loc to enhance its migration through the tight junction via binding CCR5 on brain endothelial cells It is unclear how circulating T cells cross the blood-brain barrier (BBB), and participate in the inflammation process in Alzheimer’s disease (AD). Here, we showed a significantly higher macrophage inflammatory protein-1 α (MlP-1α) expression in peripheral T lymphocytes of AD patients than age-matched healthy subjects. T cells crossing of the human brain microvascular endothelial cells (HBMECs) which constitute the BBB, were almost completely abrogated by anti-MEP-1α antibody. To identify the MEP-1α receptor on HBMECs, we investigated the CCR5 expression on HBMECs co-cultured with T cells, and the results showed an increased CCR5 expression on HBMECs. Moreover, HBMECs transfected with CCR5 resulted in increased transendothelial migration (TEM) of T cells. CCR5 antagonist (2D7 mAb) was able to block the transmigration of T cells. Further analysis revealed that the MEP-1α-CCR5 interaction triggered endothelial tight junction (TJ) ’opening’ via Rho kinase (ROCK). In addition, In vitro and in vivo results also showed that the expression of CCR5 on HBMECs and MlP-1α in T cells are correlated with Aβstimulation. More importantly, injection of A into brain hippocampus enhanced T cells transmigrating from blood to brain, however, this increased migration of T cells were effectively blocked by anti-MIP-laantibody in rat. These data are the first to suggest that the interaction between MlP-la overexpressed by T cells and CCR5 on HBMECs is involved in AD patient’s T cells migrating from blood to brain.更多还原