INTERCELLULAR-ADHESION MOLECULE-1 (ICAM-1) EXPRESSION AND ITS ROLE INNEUTROPHIL-INDUCED ISCHEMIA-REPERFUSION INJURY IN RAT-LIVER

The potential role of intercellular adhesion molecule-1 (ICAM-1) in th e pathogenesis of reperfusion injury was investigated in male Fischer rats subjected to 45 min of hepatic ischemia and 24 h of reperfusion. ICAM-1 mRNA levels increased during ischemia in the ischemic liver lob es; however, during reperfusion mRNA levels increased in both the isch emic and nonischemic lobes. Immunohistochemical evaluation indicated I CAM-1 expression only on sinusoidal lining cells in controls; ischemia -reperfusion enhanced ICAM-1 expression in the sinusoids and induced s ome expression on hepatocytes. The monoclonal anti-ICAM-1 antibody 1A2 9, but not an immunoglobulin G control antibody, administered at 1 h a nd 8 h of reperfusion (2 mg/kg) significantly attenuated liver injury as indicated by 51% lower plasma alanine aminotransferase activities a nd 32-36% less hepatic necrosis at 24 h without affecting reactive oxy gen formation by Kupffer cells and hepatic neutrophils. Although 1A29 reduced neutrophil extravasation in a glycogen peritonitis by 60%, the antibody had no significant effect on hepatic neutrophil infiltration during reperfusion. These data suggest that ICAM-1 plays a significan t role during the neutrophil-dependent injury phase after hepatic isch emia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure.