Anti-ICAM-1 blockade reduces postsinusoidal WBC adherence following cold ischemia and reperfusion, but does not improve early graft function in rat liver transplantation

Abstract Background/Aim: The present in vivo study investigated the impact of a monoclonal antibody directed against the intercellular adhesion molecule-1 (ICAM-1) on initial microvascular reperfusion injury after liver transplantation. Methods: Orthotopic, syngeneic liver transplantation including arterial reconstruction was performed in male Lewis rats after 24 h graft storage in University of Wisconsin (UW) solution at 4°C. Animals received either an anti-ICAM-1 antibody ( n =7), an IgG 1 control antibody ( n =8) or saline only ( n =7). Hepatic microvascular alterations during the initial 90 min of reperfusion were assessed using intravital fluorescence microscopy. Early graft dysfunction was determined by analysis of bile flow. Results: After treatment with anti-ICAM-1 mAb, hepatic microvascular perfusion was found improved when compared with that of IgG 1 - and saline-treated controls. In addition, anti-ICAM-1 mAb effectively reduced the number of permanently adherent white blood cells in postsinusoidal venules (284.4±59.1 mm −2 vs IgG 1 : 371.9±26.7 mm −2 and saline: 431.8±46.4 mm −2 ; p p −2 ) compared with that of IgG 1 - (215.2±11.1 mm −2 ) and saline-treated controls (226.4±14.0 mm −2 ). Measurement of hepatic uptake of fluorescent-labeled latex particles did not reveal significant differences in phagocytic activity. Finally, bile flow also did not differ between the three groups studied. Conclusion: Together these results indicate that ICAM-1 is involved in the process that mediates white blood cells adherence in postsinusoidal venules, whereas in hepatic sinusoids other mechanisms apart from ICAM-1-mediated white blood cells adherence seem to be fundamental for posttransplant white blood cells accumulation. Our data further suggest that white blood cells adherence in postsinusoidal venules via ICAM-1 does not make a major contribution to the pathogenesis of early cold ischemia/reperfusion injury after liver transplantation.