Uptake and processing of glycoproteins by isolated rat hepatic endothelial and Kupffer cells

Abstract

Mannose-(Man) and N-acetylglucosamine- (GlcNAc)-terminated glycoproteins are cleared from blood by carbohydrate-specific receptors present on both hepatic endothelial and Kupffer cells. It is not known whether the same receptors are present on each cell type or the relative contributions to glycoprotein metabolism made by Kupffer and endothelial cells. Here we report experiments where data from glycoprotein metabolism by purified populations of isolated rat hepatic endothelial and Kupffer cells have been analyzed by mathematical modelling and parameter estimation. Kupffer cells had significantly higher binding rate constants (k'21) than endothelial cells for agalactoorosomucoid (AGOR) and hyaluronidase, but lower k12 ('off-rate') indicating that Kupffer cells had higher affinities for Man/GlcNAc-terminated glycoproteins than endothelial receptors. Furthermore, although endothelial cells had similar affinities (k'21 and k12) for AGOR and hyaluronidase, the 'off-rate' of Kupffer cells was significantly greater for AGOR than for hyaluronidase, indicating that Kupffer cell receptors have lower affinity for AGOR. Internalization and ligand catabolic rates also differed between the two cell types. The data indicate that Kupffer and endothelial cells appear to have different Man/GlcNAc receptors and that the destination of a glycoprotein and its subsequent processing is determined by the structure of a glycoprotein's oligosaccharide.