title: 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: OBJECTIVE
  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 degrees C. Animals received either an anti-ICAM-1 antibody (n=7), an IgG1 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 IgG1- 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 IgG1: 371.9+/-26.7 mm(-2) and saline: 431.8+/-46.4 mm(-2); p<0.05). In contrast, the number of stagnant white blood cells in sinusoids was higher (p<0.05) in liver grafts with blocked ICAM-1 (320.6+/-17.2 mm(-2)) compared with that of IgG1- (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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University of Regensburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rentsch
authors.forename: S
authors.initials: S
authors.lastname: Post
authors.forename: P
authors.initials: P
authors.lastname: Palma
authors.forename: G
authors.initials: G
authors.lastname: Lang
authors.forename: M D
authors.initials: MD
authors.lastname: Menger
authors.forename: K
authors.initials: K
authors.lastname: Messmer
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D007511:Ischemia / Q000276:immunology* / Q000473:pathology; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000098:blood supply / Q000276:immunology / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000276:immunology*; D014181:Transplantation Immunology; D014185:Transplantation, Isogeneic
chemical_list: D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1