PROTECTIVE EFFECT OF MONOCLONAL-ANTIBODIES TO ADHESION MOLECULES ON RAT-LIVER ISCHEMIA-REPERFUSION INJURY

Background. The source of reactive oxygen species in the liver remains to be elucidated. The present study was undertaken to determine wheth er polymorphonuclear neutrophils (PMNs) can contribute to hepatic isch emia-reperfusion injury, and pretreatment with monoclonal antibodies ( mAbs)to intercellular adhesion molecule-1 (ICAM-1), lymphocyte functio n associated antigen-1 (LFA-1), aid CD 18 could improve energy metabol ism and prolong the viability of the organ. Methods. Male Wistar rats were used. Rat liver ischemia was induced by clamping blood vessels su pplying median and left lateral hepatic lobes. Monoclonal antibodies t o ICAM-1, LFA-1, or CD18 were injected Intravenously 5 minutes before inducing ischemia. To determine the effect of mAbs on the survival rat e, total hepatic ischemia was induced by clamping the hepatic artery p ortal vein, and bile duct after making a portafemoral shunt. Results. Although ischemia of the liver for 90 minutes did not permit survival of the animals, pretreatment with mAbs to ICAM-1 plus LFA-1 increased the survival rate to 57%. Pretreatment with mAb to ICAM-1 failed to in crease the survival rate. The number of PMNs in the liver increased co ntinually up to 24 hours after reperfusion after 90 minutes of ischemi a, and the expression of ICAM-1 wets enhanced 4 hours after reperfusio n. This is accompanied by a low recovery of hepatic adenosine triphosp hate and, on the contrary, a marked increase in lipid peroxide in the reperfused liver Pretreatment with mAbs suppressed the infiltration of PMNs and the elevation of lipid peroxide and enhanced the recovery of hepatic adenosine triphosphate 6, 22, or 24 hours after reperfusion. Pretreatment with mAbs also prevented the rise in serum alanine aminot ransferase level after reperfusion. Conclusions. These results suggest that PMNs contribute to ischemia-reperfusion injury in the liver 4 ho urs and more after reperfusion, and pretreatment with mAbs to adhesion molecules is useful for the prevention of ischemic liver cell injury.