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 poor ly understood. Because the adhesion molecule vascular adhesion protein -1 (VAP-1), which mediates lymphocyte binding to lymph node endotheliu m, is expressed on hepatic endothelium, it could play a role in regula ting T-cell recruitment to the liver. The aim of this study was to inv estigate the distribution of VAP-1 expression in human liver and the a bility of VAP-1 to support T-cell binding to hepatic endothelium in vi tro. Methods: Hepatic VAP-1 expression was investigated using immunohi stochemistry and specific monoclonal antibodies, and VAP-1-mediated ad hesion to hepatic endothelium was investigated with a tissue-binding a dhesion assay using human liver sections. Results: VAP-1 was expressed on sinusoidal and vascular endothelium in noninflamed liver and in in flamed liver from patients with either allograft rejection or primary biliary cirrhosis. T cells from healthy donors bound to hepatic endoth elium when added to noninflamed liver sections; this binding was inhib ited by a specific anti-VAP-1 antibody but not by antibodies to interc ellular adhesion molecule 1, lymphocyte function-associated antigen 1, or very late after activation (antigen) 4. VAP-1-mediated adhesion wa s unaffected by T-cell activation with phorbol ester. Conclusions: VAP -1 is constitutively expressed on hepatic endothelium and mediates T-c ell adhesion to hepatic endothelium in vitro. VAP-1 could play a criti cal role in regulating T-cell recirculation to the liver in vivo.