Abstract
The entry of lymphocytes into the brain is normally limited by the blood-brain barrier, however, during inflammation prominent lymphocytic infiltration occurs. In this study, we investigated the effects of nitric oxide (NO) on the adhesion of T cells to cultured human brain microvessel endothelial cells. T cell adhesion to unstimulated or tumor necrosis factor-alpha (TNF-alpha)-treated cells was quantified by counting the number of lymphocytes bound to the monolayer by light microscopy. TNF-alpha increased T cell adhesion in a time-dependent manner. Incubation of monolayers with NO donors decreased adhesion. This effect was blocked by a guanylyl cyclase inhibitor and mimicked by a cGMP agonist, and was thus dependent on the generation of cGMP. NO did not modulate adhesion molecule expression in the endothelial cells, suggesting an action on the T cells. Pre-treatment of T cells with NO or a cGMP agonist decreased binding to recombinant endothelial adhesion molecules. These findings suggest that NO can modulate the adhesion of T cells to human brain microvessel endothelial cells via a cGMP-dependent mechanism, and may thus regulate lymphocyte traffic during central nervous system inflammation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Brain / blood supply
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Cell Adhesion / drug effects
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Cell Adhesion / physiology
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Cells, Cultured
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Cyclic GMP / analogs & derivatives*
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Cyclic GMP / metabolism*
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Cyclic GMP / pharmacology
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Dose-Response Relationship, Drug
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E-Selectin / pharmacology
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Endothelial Cells / cytology*
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Enzyme Inhibitors / pharmacology
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Guanylate Cyclase / antagonists & inhibitors
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Humans
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Intercellular Adhesion Molecule-1 / pharmacology
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NG-Nitroarginine Methyl Ester / pharmacology
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Nitric Oxide / physiology*
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Synthase / antagonists & inhibitors
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Nitroprusside / pharmacology
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Nitroso Compounds / pharmacology
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Oxadiazoles / pharmacology
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Platelet Endothelial Cell Adhesion Molecule-1 / pharmacology
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Quinoxalines / pharmacology
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Signal Transduction / physiology*
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T-Lymphocytes / cytology*
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Tumor Necrosis Factor-alpha / pharmacology
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Vascular Cell Adhesion Molecule-1 / pharmacology
Substances
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1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one
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E-Selectin
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Enzyme Inhibitors
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Nitric Oxide Donors
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Nitroso Compounds
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Oxadiazoles
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Platelet Endothelial Cell Adhesion Molecule-1
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Quinoxalines
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Intercellular Adhesion Molecule-1
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2,2'-(hydroxynitrosohydrazono)bis-ethanamine
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Nitroprusside
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8-bromocyclic GMP
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Nitric Oxide
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Nitric Oxide Synthase
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Guanylate Cyclase
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Cyclic GMP
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NG-Nitroarginine Methyl Ester