Peripheral T cells overexpress MIP-1alpha to enhance its transendothelial migration in Alzheimer's disease.
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.
Man
Shu-Mei
SM
Department of Developmental Biology, Key Laboratory of Cell Biology, Ministry of Public Health of China, China Medical University, Shenyang 110001, PR China.
Ma
Yi-Ran
YR
Shang
De-Shu
DS
Zhao
Wei-Dong
WD
Li
Bo
B
Guo
Da-Wen
DW
Fang
Wen-Gang
WG
Zhu
Li
L
Chen
Yu-Hua
YH
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000473:pathology*; D016022:Case-Control Studies; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D019742:Chemokines, CC / Q000378:metabolism*; D017097:Electric Impedance; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D019713:Receptors, CCR5 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection / Q000379:methods
D016229:Amyloid beta-Peptides; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D019742:Chemokines, CC; D010446:Peptide Fragments; D019713:Receptors, CCR5; C075222:amyloid beta-protein (1-42)