Efficacy of intraportal injection of anti-ICAM-1 monoclonal antibody against liver cell injury following warm ischemia in the rat

Abstract

Background: Increased expression of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte-function-associated antigen-1 (LFA-1) has been reported to play a major role in reperfusion injury after ischemia. In the present study we tested the effects of anti-rat-ICAM-1 monoclonal antibody (1A29) on partial-liver warm ischemia in rats. Methods: Histological changes and expression of ICAM-1 and LFA-1 were investigated in rat partial-liver warm ischemia, performed by clamping hepatic hilar vessels distributing to the right lateral lobe for 30, 45, and 60 minutes. In a second study, the effects of intraportal 1A29 injection after 60 minutes of warm ischemia in the rat were examined histologically. In both studies, the liver tissue was removed for analysis 48 hours after clamping. Results: Reperfusion after 60 minutes of warm ischemia induced histological liver injury and strong expression of ICAM-1 and LFA-1, although 30 and 45 minutes of ischemia did not provoke either histological damages or the expression of ICAM-1 and LFA-1. Intraportal injection of 1A29 after 60 minutes of warm ischemia clearly suppressed liver cell injury histologically. Conclusion: Intraportal injection of 1A29 prevented the histological inflammation of an ischemic liver and may be useful in liver surgery or liver transplantation, because high concentrations can reach the target organ and nonspecific immunosuppression in other tissues and organs can be decreased.