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Nitric oxide reduces T lymphocyte adhesion to human brain microvessel endothelial cells via a cGMP-dependent pathway

Nitric oxide reduces T lymphocyte adhesion to human brain microvessel endothelial cells via a cGMP-dependent pathway

European Journal of Pharmacology 514(2-3): 91-98

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.

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Accession: 012356506

Download citation: RISBibTeXText

PMID: 15910796

DOI: 10.1016/j.ejphar.2005.03.025

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