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 alterations of sinusoidal cells in the pathogenesis of liver injury caused by hypoxia and reperfusion. In sinusoidal endothelial cells, the activity of xanthine oxidase (XOX), a cytoplasmic marker enzyme, was located cytochemically and determined biochemically. Kupffer cells, identified by their endogenous peroxidase staining, were studied with regard to changes in their ultrastructure. In our experiments, parenchymal cells were shown to be severely damaged in contrast to sinusoidal lining cells, which showed minor signs of injury. In comparison with the control group, XOX activity increased significantly in the sinusoidal endothelial cells after low-flow hypoxia; however, after reoxygenation of only 5 minutes, that activity was lower after hypoxia but higher after control perfusion. In Kupffer cells, hypoxia resulted in a strong suppression of phagocytic and endocytotic activity and in a disappearance of the lamellopodia. Kupffer cells were flattened, resembling sinusoidal endothelial cells. After reoxygenation phagocytic vesicles, lamellopodia, and cell volume of Kupffer cells increased markedly in comparison with the control group. In the hypoxia/reperfusion injury model, our observations 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.