Vascular adhesion protein 1 mediates binding of T cells to human hepatic endothelium.
OBJECTIVE
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.
McNab
G
G
Liver Research Laboratory, Queen Elizabeth Hospital, Edgbaston, Birmingham, England.
Reeves
J L
JL
Salmi
M
M
Hubscher
S
S
Jalkanen
S
S
Adams
D H
DH
D002448:Cell Adhesion; D004727:Endothelium / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D006084:Graft Rejection / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000378:metabolism / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology; D013601:T-Lymphocytes / Q000473:pathology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism / Q000502:physiology*
D019010:Vascular Cell Adhesion Molecule-1