ALTERATION OF XANTHINE-OXIDASE ACTIVITY IN SINUSOIDAL ENDOTHELIAL-CELLS AND MORPHOLOGICAL-CHANGES OF KUPFFER CELLS IN HYPOXIC AND REOXYGENATED RAT-LIVER

In the model of the perfused rat liver, we investigated the alteration s of sinusoidal cells in the pathogenesis of liver injury caused by hy poxia and reperfusion, In sinusoidal endothelial cells, the activity o f xanthine oxidase (XOX), a cytoplasmic marker enzyme, was located cyt ochemically and determined biochemically. Kupffer cells, identified by their endogenous peroxidase staining, were studied with regard to cha nges in their ultrastructure. In our experiments, parenchymal cells we re shown to be severely damaged in contrast to sinusoidal Lining cells , which showed minor signs of injury. In comparison with the control g roup, XOX activity increased significantly in the sinusoidal endotheli al cells after low-flow hypoxia; however, after reoxygenation of only 5 minutes, that activity was lower after hypoxia but higher after cont rol perfusion. In Kupffer cells, hypoxia resulted in a strong suppress ion of phagocytic and endocytotic activity and in a disappearance of t he lamellopodia. Kupffer cells were flattened, resembling sinusoidal e ndothelial cells. After reoxygenation phagocytic vesicles, lamellopodi a, and cell volume of Kupffer cells increased markedly in comparison w ith the control group. In the hypoxia/reperfusion injury model, our ob servations revealed significant alterations of sinusoidal lining cells . It appears that sinusoidal endothelial cells respond to the hypoxic phase by producing oxygen-derived free radicals and that Kupffer cells respond to the subsequent reperfusion phase by activation followed by the release of toxic mediators.