The cysteine-rich domain of the macrophage mannose receptor is a multispecific lectin that recognizes chondroitin sulfates A and B and sulfated oligosaccharides of blood group Lewis(a) and Lewis(x) types in addition to the sulfated N-glycans of lutropin

Thc mannose receptor (MR) is an endocytic protein on macrophages and dendri tic cells, as well as on hepatic endothelial, kidney mesangial, tracheal sm ooth muscle, and retinal pigment epithelial cells. The extracellular portio n contains two types of carbohydrate-recognition domain (CRD), eight membra ne-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR) . The former bind mannose-, N-acetylglucosamine-, and fucose-terminating ol igosaccharides, and mall be important in innate immunity ton-ards microbial pathogens, and in antigen trapping for processing and presentation in adap tive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitar y hormones and may have a role in hormonal clearance. A second feature of C ys-MR is binding to macrophages in marginal zones of the spleen, and to B c ell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel cl asses of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of th e type found on proteoglycans produced by cells of the immune system, and s ulfated blood group chains. We further demonstrate that Cys-MR interacts wi th cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may v ariously regulate the trafficking and function of MR-bearing cells.