HUMAN BETA-GLUCURONIDASE - INVIVO CLEARANCE AND INVITRO UPTAKE BY A GLYCOPROTEIN RECOGNITION SYSTEM ON RETICULOENDOTHELIAL CELLS

Previously reported studies demonstrated that infused human placental .beta.-glucuronidase is rapidly cleared from rat plasma and localizes predominantly in rat liver. Prior treatment of the enzyme with sodium metaperiodate converted the enzyme to a very slow clearance form. The clearance system apparently recognized the carbohydrate structure of the glycoprotein hydrolase. Glycosyl specificity is defined and the cell type(s) involved in the clearance process. Clearance of infused human .beta.-glucuronidase was blocked by simultaneous infusion of glycoproteins which had mannose or N-acetylglucosamine in their exposed nonreducing position, or by some simple sugars (.alpha.-methylmannoside, mannose or L-fucose) which block clearance of these glycoproteins. Two immunohistochemical techniques demonstrated preferential localization of human .beta.-glucuronidase in sinusoidal lining cells (nonparenchymal cells) in rat liver. Human placental .beta.-glucuronidase was taken up by isolated rat alveolar macrophages by the carbohydrate-mediated glycoprotein uptake system recently demonstrated in these cells. This isolated cell uptake system appears to have the same specificity as the system for plasma clearance of infused human placental .beta.-glucuronidase in the intact rat. In vivo clearance studies and studies of enzyme uptake by isolated rat macrophages suggest that a mannose/N-acetylglucosamine-glycoprotein uptake system is expressed on fixed tissue macrophages in the rat, and that this system mediates plasma clearance of infused human placental .beta.-glucuronidase.