The uptake of native and desialylated glucocerebrosidase by rat hepatocytes and Kupffer cells

Human glucocerebrosidase is cleared from rat circulation after intravenous administration with a half-life of 21 minutes. The enzyme retains at least 85% of its activity following desialylation with neuraminidase and the half-life of the desialylated enzyme is 1.2 minutes. Asialo-orosomucoid inhibits the disappearance of the desialylated enzyme from the blood. Untreated enzyme is taken up by both Kupffer cells and hepatocytes while desialylated enzyme is cleared predominantly by hepatocytes and the uptake by Kupffer cells is reduced. These findings indicate that both Kupffer cells and hepatocytes take up a lysosomal enzyme and removal of sialic acid augments uptake by hepatocytes and decreases uptake by Kupffer cells.