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L3促进T淋巴细胞穿过脑微血管内皮细胞单层

Increased migration of T cells through brain microvascular endothelial cells monolayer dependent on CCL3

中文摘要英文摘要

有研究表明,T细胞可能参与阿尔茨海默氏病(AD)免疫过程,但T细胞如何穿过血脑屏障内皮细胞紧密连接,到达脑内还不清楚。我们研究曾发现,AD病人外周血T淋巴细胞穿过人脑微血管内皮细胞(HBMEC)单层能力高于同龄正常人,其T淋巴细胞巨噬细胞炎症蛋白1α(MIP-1α, 也称CCL3)表达明显增高。为进一步在体外研究促使T淋巴细胞穿过HBMEC单层的机制,选取重组人MIP-1α(rhMIP-1α)作用于HBMEC,同时选用高表达MIP-1α的人急性白血病T淋巴细胞(6T-CEM)作为模式细胞,与HBMEC共同温育。发现rhMIP-1α可促进6T-CEM细胞穿过HBMEC单层,并使HBMEC单层紧密连接结构发生改变。在6T-CEM细胞或rhMIP-1α与HBMEC单层单独温育过程中,均引起HBMEC单层CCR5表达变化。提示MIP-1α可能通过与HBMEC单层上CCR5相互作用介导T淋巴细胞穿过HBMEC单层。

It has been showed that T lymphocytes might participate in the inflammation process in Alzheimer’s disease (AD), however, it is unclear how circulating T cells cross the blood-brain barrier (BBB). We have showed the stronger ability to migrate through human brain microvascular endothelial cells (HBMECs) and a significantly higher macrophage inflammatory protein-1α (MIP-1α, CCL3) expression in peripheral T lymphocytes of AD patients than age-matched healthy subjects. In order to explore the mechanism of the transendothelial migration of T lymphocytes further, rhMIP-1α or 6T-CEM, the cell line of human lymphoblastic leukemia which highly expressed MIP-1α, were incubated with HBMEC monolayer separately. It was showed that rhMIP-1α could enhance the migration of 6T-CEM cells through HBMEC monolayer and disrupt the tight junction of HBMEC. The expressions of CC chemokine receptor 5 (CCR5) on HBMECs which incubated with rhMIP-1α or 6T-CEM cells were detected. These data suggested that MIP-1α might promote the transendothelial migration of T lymphocytes by interacting with CCR5 on HBMEC monolayer.

陈誉华、尚德淑

基础医学神经病学、精神病学分子生物学

L3人脑微血管内皮细胞紧密连接蛋白ZO-1趋化因子受体5

L3human brain microvascular endothelial celltight junction protein ZO-1chemokine receptor 5

陈誉华,尚德淑.L3促进T淋巴细胞穿过脑微血管内皮细胞单层[EB/OL].(2007-12-25)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/200712-661.点此复制

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