Lymphocyte migration into the CNS modelled in vitro: roles of LFA-1, ICAM-1 and VLA-4.
We examined the changes in intercellular adhesion molecule-1 (ICAM-1) expression on brain endothelium in response to tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). ICAM-1 is normally present on these cells and is induced over 24 hr by both cytokines with a time-course which matches enhancement in lymphocyte adhesion. Anti-lymphocyte function-associated antigen-1 (anti-LFA-1) (CD11a), anti-very late antigen-4 (anti-VLA-4) (CD49d) and anti-CD18 block binding of mitogen-activated lymphocytes to brain endothelium and the effects of anti-LFA-1 and anti-VLA-4 are additive. Anti-ICAM-1 does not however block adhesion, nor does depletion of endothelial ICAM-1 reduce lymphocyte binding. Titration of the interacting cells indicated that the antibody blocking is due to interference in the endothelial/lymphocyte interaction. None of the antibodies affect the binding of non-activated lymphocytes, which is itself normally much lower than that of activated cells. The time at which lymphocyte adhesiveness is greatest for the endothelium corresponds with the time at which the lymphocytes express highest levels of LFA-1 and VLA-4. The data show a role for LFA-1 and VLA-4 in the early interaction of activated lymphocytes with brain endothelium. Kinetic studies indicate that the ligand for VLA-4 is VCAM-1. The ligand for LFA-1 could not be determined with certainty, but if it is ICAM-1, the levels of ICAM-1 on brain endothelium are not critical.
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Department of Neuropathology, Institute of Psychiatry, London, U.K.
Rahman
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Pryce
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Tamatani
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Miyasaka
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D000818:Animals; D001921:Brain / Q000276:immunology*; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D016029:Receptors, Very Late Antigen / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D016029:Receptors, Very Late Antigen; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma