Cytokine-regulated adhesion between encephalitogenic T lymphocytes and cerebrovascular endothelial cells.
Adhesive interactions between murine cerebrovascular endothelial cells (EC) which comprise the blood-brain barrier (BBB) and myelin basic protein (MBP)-specific encephalitogenic T lymphocytes were investigated. Adhesion was assessed by measuring the percent attachment of 51Cr-labeled T cells to EC monolayers. The basal level adhesion (20-35%) was significantly up-regulated by treating EC with recombinant murine gamma interferon (IFN-gamma), interleukin-1 alpha (IL-1 alpha) and/or tumor necrosis factor-alpha (TNF alpha). The ability of these cytokines to modulate adhesion was dose- and time-dependent and could be detected as early as 1 h after treatment. The expression of intercellular adhesion molecule-1 (ICAM-1) by EC was examined by immunofluorescence staining and ELISA. Although all unstimulated EC cultures expressed ICAM-1, treatment of EC with the above cytokines dramatically up-regulated the level of ICAM-1 expression in a dose- and time-dependent fashion similar to that observed in the adhesion assays. Treatment of EC with transforming growth factor-beta 1 (TGF beta) down-regulated the level of T cell adhesion on untreated EC in a dose-dependent manner. Pretreatment of EC with TGF beta also partially inhibited the up-regulation of adhesion induced by IFN-gamma, IL-1 alpha and/or TNF alpha. TGF beta had no effect on the up-regulation of ICAM-1 expression induced by IFN-gamma, IL-1 alpha and/or TNF alpha. These results indicate that in addition to ICAM-1, other molecules may be involved in adhesion of encephalitogenic T cells to the EC comprising the cerebral vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)
McCarron
R M
RM
Stroke Branch, NINDS, National Institutes of Health, Bethesda, MD 20892.
Wang
L
L
Racke
M K
MK
McFarlin
D E
DE
Spatz
M
M
D000818:Animals; D001921:Brain / Q000098:blood supply*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D016207:Cytokines; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1