MODULATION OF ISCHEMIA-REPERFUSION-INDUCED HEPATIC-INJURY BY KUPFFER CELLS

To elucidate the role of Kupffer cells in ischemia-reperfusion-induced hepatic injury, hepatic injury induced by ischemia-reperfusion was an alyzed after modulation of Kupffer cell function. Ischemia of the live r was performed by occlusion of both the portal vein and hepatic arter y, which enter into the left lateral and median lobes of the liver. Bl ood flow in the ischemic lobe was reduced, in contrast to an increased blood flow in,the nonischemic lobe during occlusion of the veins. Alt hough hepatocyte damage was not demonstrated by ischemia for <60 min, hepatic injury was found after reperfusion of the liver, and activatio n of Kupffer cells was morphologically demonstrated by electron micros copies. Suppression of Kupffer cells, induced by previous administrati on of gadolinium chloride or latex particles, reduced the grade of hep atic injury induced by ischemia-reperfusion. On the other hand, stimul ation of Kupffer cell phagocytosis, induced by administration of latex particles at the time of reperfusion, aggravated the ischemia-reperfu sion-induced hepatotoxicity, which was then reduced by simultaneous ad ministration of superoxide dismutase. Kupffer cells, isolated from the rats treated with the ischemia-reperfusion procedure, have been found to release increased amounts of oxygen radical intermediaries. These results suggest that hepatic injury induced by ischemia-reperfusion is modulated by the function of Kupffer cells and that superoxide anion released from Kupffer cells could play an important role in ischemia-r eperfusion hepatic injury.