HOME
Return to Table of Contents
005 DIFFERENTIAL EFFECT OF ANTI-ALPHA4 INTEGRIN AND ANTI-VASCULAR ADHESION PROTEIN-1 ANTIBODIES ON THE CONCANAVALIN A-INDUCED HEPATITIS WY Lee, P Kubes Hepatitis derived by concanavalin A (Con A) in mice is well known to be a lymphocyte-mediated disease. It has been reported that Th1 and Th2 lymphocytes use alpha4 integrin and vascular adhesion protein (VAP)-1, respectively, to adhere within the hepatic sinusoids. Therefore, we investigated whether the monoclonal antibodies against them can ameliorate the Con A-induced hepatic damage in vivo, and can inhibit the change in the hepatic lymphocyte profile derived by Con A. Saline or antibodies to alpha4 integrin (PS/2, 100 µg) or VAP-1 (cocktail of 7-88 and 7-106, 50 µg each) were administered intravenously 30 min before Con A (13, 15, or 20 mg/kg, i.v.) administration. Con A treatment markedly increased the serum level of alanine aminotransferase (ALT) in a dose-dependent manner. Interestingly, an intermediate dose of Con A (15 mg/kg) induced liver injury was attenuated by anti-VAP-1 antibody, while anti-alpha4 integrin antibody enhanced Con A-induced injury. However, neither antibody affected the increase in ALT level at 24 h after Con A administration. In immunophenotyping analysis using flow cytometry, we observed a massive infiltration of NK and CD3 T cells and a decrease in NKT cells by Con A. Pretreatment with anti-VAP-1 antibodies attenuated the increase in CD3 T cells, but did not influence the NK and NKT cells. Con A treatment increased the number of both CD4 and CD8 T lymphocytes, and pretreatment with anti-VAP-1 antibody prevented the increase of both. Anti-alpha4 integrin antibody did not reduce CD4 or CD8 lymphocyte recruitment into the liver. Our findings suggest that anti-VAP-1 antibody ameliorates the Con A-induced hepatic injury, which is associated with its blocking the infiltration of CD4 and CD8 lymphocytes.
Immunology Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta
This study was supported by CIHR and the CIHR training program