ENDOCYTOSIS OF RICIN BY RAT-LIVER CELLS INVIVO AND INVITRO IS MAINLY MEDIATED BY MANNOSE RECEPTORS ON SINUSOIDAL ENDOTHELIAL-CELLS

Upon intravenous injection into rats, the plant toxin ricin was rapidl y cleared from the circulation by the liver. Among the different liver cell populations, most of the injected ricin associated with the sinu soidal endothelial cells (EC), whereas the liver parenchymal cells (PC ) and Kupffer cells (KC) yielded minor contributions to the total live r uptake in vivo. Co-injection of mannan strongly inhibited ricin upta ke by the EC, showing that it was mediated by mannose receptors. On th e other hand, co-injection of lactose, which inhibits the galactose-sp ecific association of ricin with cells, enhanced ricin uptake by the E C. The carbohydrate-dependency of the EC contribution to the uptake of ricin in vivo was reflected in the carbohydrate-dependency of the upt ake in vivo by whole liver. In vitro, the EC also endocytosed ricin mo re efficiently than did the PC or KC. Whereas uptake in vitro in the E C was mainly mannose-specific, uptake in the two other cell types was mainly galactose-specific. Western blotting showed that the mannose re ceptors of liver non-parenchymal cells are identical with the mannose receptor previously isolated from alveolar macrophages. The mannose re ceptors are expressed at a higher level in EC than in KC. Ligand blott ing showed that, in the presence of lactose, the mannose receptor is t he only protein in the EC that binds ricin, and the binding is mannose -specific and Ca2+-dependent.