Studies on the fate of defined asialoglycoproteins in the circulation of the mouse.

Asialoglycoproteins injected into the tail vein of mice accumulated rapidly in the liver, as found in rats and rabbits by other authors, whereas the native glycoprotein remained in the serum for much longer periods of time. Histological examination of liver sections after the injection of radiolabelled asialoglycoproteins failed to show any binding to the hepatocyte membrane. However, silver grains were observed in the sinuses of the liver and often appeared to be bound to the sinus wall. In addition, small amounts of label in the reticulo-endothelial system of the spleen were observed. A comparison in the uptake of asialoglycoproteins by the liver, between those with alkali-labile galactose-containing (AL) chains and those with alkali-stable galactose-containing (AS) chains, showed that the former were taken up more slowly. There was no correlation between total galactose content and rate of hepatic uptake. Asialoglycoproteins with AS chains could not inhibit the uptake in the liver of those with AL chains. However, when the order was reversed, the uptake of AS containing asialoglycoproteins was inhibited by 50%. Different mechanisms to explain these results are discussed.