The Macrophage Mannose Receptor: Current Status

Abstract

Sugar-specific recognition of oligosaccharide chains present on macromolecules and particles has emerged as an important mechanism by which macrophages carry out a variety offunctions including host defense, molecular scavenging, and cell-cell recognition. Among the oligosaccharide determinants that are recognized by macrophages, terminal mannose residues are the most thoroughly studied. More than a decade ago, in vivo experiments showed that a variety of glycoproteins bearing high mannose chains, including the lysosomal enzyme {j-glucuronidase, were rapidly and specifically cleared from the bloodstream after intravenous infusion (1). It is now widely appreciated that in vivo clearance of mannose glycoconjugates is mediated by a receptor found in liver Kupffer and endothelial cells and in mononuclear phagocytes (2). With the exception of lysosomal hydrolases, which possess high mannose chains as a remnant of the mannose-phosphate targeting marker, glycoproteins and membrane glycoconjugates of most higher organisms bear processed or complex N-linked oligosaccharide chains (3). As such, mannose is nearly always relegated to a penultimate or more inferior position in the carbohydrate structure. Lower organisms, however, including many infectious agents, have little facility to process N-linked oligosaccharide chains and, consequently, express abundant mannose, glucose, and other sugars on their surfaces. It is not surprising, then, that higher organisms have evolved sugar-specific recognition molecules as part oftheir host-defense system. Macrophages recognize, in addition to mannose and L-fucose, molecules and particles bearing galactose, glucose, and N-acetylneuraminic acid residues (2). The mannose receptor has served as an excellent model for studies of receptor recycling in the macrophage. The availability of several high affinity ligands and anti-receptor antibodies have permitted a detailed analysis of receptor movement in macrophages. {j-Glucuronidase, a lysosomal glycosidase that can be easily purified from rat preputial glands, and mannose-derivitized bovine serum albumin (mannoseBSA) , bind the mannose receptor with high affinity. Many other glycoconjugates have been used as ligands as well, including ricin A-chain, yeast mannan and invertase, ovalbumin, and ribonuclease B. Binding and internalization studies have shown that the mannose receptor is both phagocytic (4)