Intercellular adhesion molecule 1 (ICAM‐1) expression and its role in neutrophil‐induced ischemia‐reperfusion injury in rat liver

The potential role of intercellular adhesion molecule‐1 (ICAM‐1) in the 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 lobes; however, during reperfusion mRNA levels increased in both the ischemic and nonischemic lobes. Immunohistochemical evaluation indicated ICAM‐1 expression only on sinusoidal lining cells in controls; ischemia‐reperfusion enhanced ICAM‐1 expression in the sinusoids and induced some expression on hepatocytes. The monoclonal anti–ICAM‐1 antibody 1A29, but not an immunoglobulin G control antibody, administered at 1 h and 8 h of reperfusion (2 mg/kg) significantly attenuated liver injury as indicated by 51% lower plasma alanine aminotransferase activities and 32–36% less hepatic necrosis at 24 h without affecting reactive oxygen 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 significant role during the neutrophil‐dependent injury phase after hepatic ischemia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure. J. Leukoc. Biol . 57: 368–374; 1995.