Vascular adhesion protein 1 mediates binding of T cells to human hepatic endothelium.
BACKGROUND & AIMS: Molecules that regulate T-cell adhesion to hepatic endothelium and thereby recirculation of T cells to the liver are poorly understood. Because the adhesion molecule vascular adhesion protein-1 (VAP-1), which mediates lymphocyte binding to lymph node endothelium, is expressed on hepatic endothelium, it could play a role in regulating T-cell recruitment to the liver. The aim of this study was to investigate the distribution of VAP-1 expression in human liver and the ability of VAP-1 to support T-cell binding to hepatic endothelium in vitro. METHODS: Hepatic VAP-1 expression was investigated using immunohistochemistry and specific monoclonal antibodies, and VAP-1-mediated adhesion to hepatic endothelium was investigated with a tissue-binding adhesion assay using human liver sections. RESULTS: VAP-1 was expressed on sinusoidal and vascular endothelium in non-inflamed liver and in inflamed liver from patients with either allograft rejection or primary biliary cirrhosis. T cells from healthy donors bound to hepatic endothelium when added to noninflamed liver sections; this binding was inhibited by a specific anti-VAP-1 antibody but not by antibodies to intercellular adhesion molecule 1, lymphocyte function--associated antigen 1, or very late after activation (antigen) 4. VAP-1--mediated adhesion was unaffected by T-cell activation with phorbol ester. CONCLUSIONS: VAP-1 is constitutively expressed on hepatic endothelium and mediates T-cell adhesion to hepatic endothelium in vitro. VAP-1 could play a critical role in regulating T-cell recirculation to the liver in vivo.[1]References
- Vascular adhesion protein 1 mediates binding of T cells to human hepatic endothelium. McNab, G., Reeves, J.L., Salmi, M., Hubscher, S., Jalkanen, S., Adams, D.H. Gastroenterology (1996) [Pubmed]
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