COMPLEMENT ACTIVATES KUPFFER CELLS AND NEUTROPHILS DURING REPERFUSIONAFTER HEPATIC ISCHEMIA

The hypothesis that complement factors may be involved in the postisch emic activation of Kupffer cells (KC) and polymorphonuclear neutrophil s (PMN) was investigated in a model of hepatic ischemia (45 min) and r eperfusion in male Fischer rats in vivo. Depletion of serum complement before ischemia resulted in a significant attenuation of the KC-induc ed oxidant stress (enhanced oxidation of plasma glutathione) and also prevented the accumulation of PMNs in the liver during the initial rep erfusion period of 1 h. Complement activation through injection of cob ra venom factor (CVF; 75 mug CVF/kg) also induced enhanced oxidation o f plasma glutathione and accumulation of PMNs in the liver. Isolation of KC and PMNs from the liver 1 h after CVF treatment demonstrated a s imilar priming effect for stimulation with phorbol myristate acetate a nd opsonized zymosan as was observed in the postischemic liver. Comple ment-depleted animals and animals pretreated with the soluble human co mplement receptor type 1 (BRL 55730; 22.5 mg/kg) accumulated significa ntly less PMNs in the postischemic livers during longer reperfusion pe riods (24 h) and sustained significantly less injury. It is concluded that complement is involved in the induction of a KC-induced oxidant s tress, the priming of KC and PMNs for enhanced reactive oxygen generat ion, and the continuous accumulation of PMNs in the liver during reper fusion.