DOWN-REGULATION OF MANNOSE RECEPTORS ON MACROPHAGES AFTER INFECTION WITH LEISHMANIA-DONOVANI

Macrophages express a mannose-specific endocytosis receptor that binds and internalizes mannose-terminated glycoproteins. Infection of mouse peritoneal macrophages with Leishmania donovani resulted in a decrease in mannose-receptor activity. With I-125-labelled beta-glucuronidase as ligand, a 2-fold decrease in uptake rate was observed in infected cells, with no change in K(uptake). Cell-surface binding of I-125-mannose-BSA was diminished 2.5-fold after infection. The decrease in ligand binding appeared to be due to a decrease in the number of sites, with no change in affinity. Elimination of parasites from infected cells by treatment with neoglycoprotein-conjugated methotrexate resulted in an increase in receptor number. Cycloheximide suppressed the drug-treatment-mediated rise in receptor number in infected macrophages. A decrease in receptor activity was also observed in liver Kupffer cells isolated from parasite-infected mice. Binding of ligand by another carbohydrate receptor, the mannose 6-phosphate receptor, was not altered by infection. Phagocytosis of yeast cells was also not altered. These results suggest that mannose receptor synthesis in macrophages is specifically suppressed after infection with Leishmania parasites.