Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9921324 | European Journal of Pharmacology | 2005 | 8 Pages |
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-α)-treated cells was quantified by counting the number of lymphocytes bound to the monolayer by light microscopy. TNF-α 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.
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Authors
Donald Wong, Rukmini Prameya, Vivian Wu, Katerina Dorovini-Zis, Steven R. Vincent,