In vivo uptake of Cu, Zn superoxide dismutase. Morphological evidence for preferential endocytosis and accumulation by sinusoidal liver cells.

Bovine Cu, Zn superoxide dismutase (SOD), conjugated to colloidal gold, was intravenously administered to rats and its distribution studied by electron microscopy. Liver was the preferential site of accumulation of gold-labelled SOD. Among liver cells types, Kupffer and endothelial cells showed the presence of the protein earlier than hepatocytes. Uptake by kidney showed slower kinetics than liver. No uptake by heart could be detected. The gold-labelled SOD was localized inside coated pits, coated vesicles and other non-coated endocytic compartments. Absence of binding by BSA-gold complexes and competition between free SOD and the gold-labelled one demonstrated the specificity of the uptake process. Our morphological evidences suggest that in vivo internalization of SOD occurs most likely through receptor-mediated endocytosis.