Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication. | ||||||||
|
Peripheral T cells overexpress MIP-1alpha to enhance its transendothelial migration in Alzheimer's disease.Man SM, Ma YR, Shang DS, Zhao WD, Li B, Guo DW, Fang WG, Zhu L, Chen YH Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110001, PR China. 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-1alpha (MIP-1alpha) 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-1alpha antibody. MIP-1alpha induced the expression of CCR5, a potential MIP-1alpha 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-1alpha-CCR5 interaction promoted T cells transendothelial migration via ROCK (Rho kinase). Furthermore, Abeta injection into rats' hippocampus induced MIP-1alpha overexpression accompanied with increased T lymphocytes occurrence in the brain cortex and this enhanced T cells entry was effectively blocked by anti-MIP-1alpha antibody. These data are the first to suggest that the interaction between MIP-1alpha overexpressed by T cells and CCR5 on HBMECs is involved in AD patients' T cells migrating from blood to brain. Published 26 February 2007 in Neurobiol Aging, 28(4): 485-96.
© 2004-2008 Alzheimer's Disease Research Today. All Rights Reserved. |
| ||||||
