Beta-amyloid peptide-induced blood-brain barrier disruption facilitates T-cell entry into the rat brain.
Activated T-lymphocytes can migrate through the blood-brain barrier (BBB) and are able to invade the central nervous system (CNS). In the present study, we investigated whether disruption of the BBB leads to enhanced T-cell migration into the CNS. Amyloid-beta peptide 25-35 (A beta) or tumor necrosis factor-alpha (TNFalpha) were administered into the right common carotid artery of adult male Wistar rats. The agents were administered either alone, or were followed by a cell suspension of exogenously activated T-cells. Rats of other groups received activated or non-stimulated T-lymphocytes only. Sagittal brain sections were analyzed with immunohistochemistry of CD3 to reveal the presence of T-lymphocytes within the CNS parenchyma. Administration of activated T-cells alone led to T-cell migration into the brain. Infusion of either substances (A beta or TNFalpha) resulted in T-cell invasion of the CNS even when no exogenous T-cells were added. Infusion of either of the agents together with T-lymphocytes generated a more intense T-lymphocyte migration than in the other groups. Electron microscopic analysis and Evans-blue extravasation studies confirmed parallel disruption of the BBB. Our study demonstrates that A beta and TNFalpha induce enhanced T-lymphocyte migration towards the brain. This effect may be attributed at least partly to dysfunctioning of the BBB, but other mechanisms are also possible.
Farkas
Ibolya G
IG
Department of Anatomy, Histology and Embryology, University of Szeged, Hungary. farkasi@anat-fm.szote.u-szeged.hu
Czigner
Andrea
A
Farkas
Eszter
E
Dobó
Endre
E
Soós
Katalin
K
Penke
Botond
B
Endrész
Valéria
V
Mihály
András
A
D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000473:pathology; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000648:ultrastructure; D017252:CD3 Complex / Q000032:analysis; D002490:Central Nervous System / Q000276:immunology; D005070:Evans Blue; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D010446:Peptide Fragments / Q000494:pharmacology* / Q000633:toxicity; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D017252:CD3 Complex; D010446:Peptide Fragments; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); D005070:Evans Blue