Peripheral T cells overexpress MIP-1α to enhance its transendothelial migration in Alzheimer's disease
Peripheral T cells overexpress MIP-1α to enhance its transendothelial migration in Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2006.02.013
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发表时间：
2007-04-01
影响因子：
4.2
通讯作者：
Chen, Yu-Hua
中科院分区：
文献类型：
--
作者：
Man, Shu-Mei;Ma, Yi-Ran;Chen, Yu-Hua
目前尚不清楚循环 T 细胞如何穿过血脑屏障 (BBB) 并参与阿尔茨海默病 (AD) 的炎症过程。在这里，我们发现 AD 患者外周 T 淋巴细胞中巨噬细胞炎症蛋白 1 α (MIP-1 α) 的表达显着高于年龄匹配的对照组。 T 细胞穿过构成 BBB 的人脑微血管内皮细胞 (HBMEC)。几乎完全被抗 MIP-1 α 抗体消除。 MIP-1 α 诱导 HBMEC 上 CCR5（一种潜在的 MIP-1 α 受体）的表达。转染 CCR5 的 HBMEC 导致 T 细胞跨内皮迁移增加。 CCR5 拮抗剂 (2D7 mAb) 阻断 T 细胞迁移。 MIP-1 α-CCR5 相互作用通过 ROCK（Rho 激酶）促进 T 细胞跨内皮迁移。此外，将Aβ注射到大鼠海马中会诱导MIP-1α过度表达，同时大脑皮层中T淋巴细胞的出现增加，并且这种增强的T细胞进入可被抗MIP-1α抗体有效阻断。这些数据首次表明，T 细胞过表达的 MIP-1 α 与 HBMEC 上的 CCR5 之间的相互作用参与了 AD 患者的 T 细胞从血液迁移到大脑的过程。 (c) 2006 Elsevier Inc. 保留所有权利。
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 significantly higher macrophage inflammatory protein-1 alpha (MIP-1 alpha) expression in peripheral T lymphocytes of AD patients than age-matched controls. T cells crossing of the human brain microvascular endothelial cells (HBMECs) which constitute the BBB. were almost completely abrogated by anti-MIP-1 alpha antibody. MIP-1 alpha induced the expression of CCR5, a potential MIP-1 alpha receptor, on HBMECs. HBMECs tranfected with CCR5 resulted in increased T cells transendothelial migration. CCR5 antagonist (2D7 mAb) blocked the T cells transmigration. The MIP-1 alpha-CCR5 interaction promoted T cells transendothelial migration via ROCK (Rho kinase). Furthermore, A beta injection into rats' hippocampus induced MIP-1 alpha overexpression accompanied with increased T lymphocytes occurrence in the brain cortex and this enhanced T cells entry was effectively blocked by anti-MIP-1 alpha antibody. These data are the first to suggest that the interaction between MIP-1 alpha overexpressed by T cells and CCR5 on HBMECs is involved in AD patients' T cells migrating from blood to brain. (c) 2006 Elsevier Inc. All rights reserved.