A MONOCLONAL-ANTIBODY AGAINST ICAM-1 SUPPRESSES HEPATIC ISCHEMIA-REPERFUSION INJURY IN RATS

Since intercellular adhesion molecule-1 (ICAM-1) has been reported to play a major role in reperfusion injury after ischemia, we estimated t he effects of an anti-rat ICAM-1 monoclonal antibody (1A29) on hepatic ischemia-reperfusion injury in rats. Partial liver ischemia was achie ved by clamping hepatic hilar vessels supplying the cephalad three lob es of the liver for 90 min. An intraportal injection of 1A29 was given 5 min after revascularization (n = 28), and saline was injected in co ntrol rats (n = 28). Changes in the proportion of liver necrosis, hepa tic tissue blood flow, serum liver enzymes and liver neutrophil seques tration were analyzed at 6, 24, 48 and 72 h after revascularization. T he intraportal injection of 1A29 significantly reduced the hepatocellu lar necrosis, restored the hepatic tissue blood flow at 24, 48 and 72 h of reperfusion (p < 0.05 or p < 0.01), and significantly suppressed the levels of serum liver enzymes at all time points during reperfusio n (p < 0.01, respectively). The 1A29 treatment significantly reduced t he number of neutrophils at the pericentral area, while those at the p eriportal area were similar in the two groups. The results suggested t hat ICAM-1 plays an important role in the development of hepatic ische mia-reperfusion injury, and that 1A29 reduced the injury possibly caus ed by cytotoxic inflammatory responses, based on neutrophil adherence to pericentral sinusoids.