The Application Of Anti-ICAM-1 Monoclonal Antibody In The Liver Transplantation Rejection And Hepatic Cellular Apoptosis

Liver transplantation has been recognized as the most effective approach in the treatment of the end-stage liver disease worldwide. Like other organ transplantation surgeries, the rejection is a major concern for liver transplantation. Currently, in the transplantation research, it is a common concern to control the rejection and to avoid the complications induced by immuno-suppression. In this study, we used anti-ICAM-1 monoclonal antibody to block the binding of ICAM-1 and its ligand. The role of the adherence molecule in the rejection was examined. Meanwhile, we tried to understand the relationship between hepatic cellular apoptosis and rejection through observations about the hepatic cellular apoptosis in the liver transplantations.Objectives: To compare the effect of 1A29,Cyclosporine A (CsA) and their combination on the rejection reaction of the mouse model undergoing liver transplantation. To observe the degree of hepatic cellular apoptosis under different cases of transplantation rejections.Methods: We established stable mouse liver transplantation model. Mice from the same strain were used as control group since they are genetically identical (theoretically no rejection). Post-transplantation host-anti-transplant rejection model was established using mice from different strains. That was the experiment group. The effects of 1A29, CsA and their combination against transplantation rejection were examined in both groups. Hepatic cellular apoptosis observed in the above rejections were recorded and evaluated.Results: No rejection was observed in transplantations between the mice of the same strain (SD -^ SD), while transplantation from mouse of different strains (Wistar -"SD) showed different levels of rejection. Biochemical test showed a significant increase in the level of enzyme spectrum and bill in the blood. An apparent pathology change due to rejection was also detected. 2, Optimal dose of CsA (lOmg/kg body weight) effectivelysuppressed rejection while optimal dose of 1A29 did not. Sub-optimal dose of CsA (3mg/kg) had no effect on rejection when used alone. As contrast, the combination of sub-optimal dose of CsA and optimal dose of 1A29 inhibited rejection. 3, There was a significant increase of the hepatic apoptosis in the transplanted liver rejected by the recipient, however, the level of cellular apoptosis showed no significant change in the transplanted liver without rejection due to immnosuppressor.Conclusions: 1. Genetic difference between the mice is the key factor inducing liver post-transplantation rejection. 2. The application of CsA could effectively inhibit the rejection in the mouse liver transplantation. 3. 1A29 and CsA could synergistically inhibit transplantation rejection even though 129A had no effect by itself. 4. Transplantation rejection and hepatic apoptosis were closely correlated. 5. Hepatic apoptosis was not influence by 1A29.