title: 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.
abstract: The mannose receptor (MR) is an endocytic protein on macrophages and dendritic cells, as well as on hepatic endothelial, kidney mesangial, tracheal smooth muscle, and retinal pigment epithelial cells. The extracellular portion contains two types of carbohydrate-recognition domain (CRD): eight membrane-proximal C-type CRDs and a membrane-distal cysteine-rich domain (Cys-MR). The former bind mannose-, N-acetylglucosamine-, and fucose-terminating oligosaccharides, and may be important in innate immunity towards microbial pathogens, and in antigen trapping for processing and presentation in adaptive immunity. Cys-MR binds to the sulfated carbohydrate chains of pituitary hormones and may have a role in hormonal clearance. A second feature of Cys-MR is binding to macrophages in marginal zones of the spleen, and to B cell areas in germinal centers which may help direct MR-bearing cells toward germinal centers during the immune response. Here we describe two novel classes of carbohydrate ligand for Cys-MR: chondroitin-4 sulfate chains of the type found on proteoglycans produced by cells of the immune system, and sulfated blood group chains. We further demonstrate that Cys-MR interacts with cells in the spleen via the binding site for sulfated carbohydrates. Our data suggest that the three classes of sulfated carbohydrate ligands may variously regulate the trafficking and function of MR-bearing cells.
authors.affiliation: The Glycosciences Laboratory, Imperial College School of Medicine, Northwick Park Hospital, Harrow HA1 3UJ, United Kingdom.
authors.forename: C
authors.initials: C
authors.lastname: Leteux
authors.forename: W
authors.initials: W
authors.lastname: Chai
authors.forename: R W
authors.initials: RW
authors.lastname: Loveless
authors.forename: C T
authors.initials: CT
authors.lastname: Yuen
authors.forename: L
authors.initials: L
authors.lastname: Uhlin-Hansen
authors.forename: Y
authors.initials: Y
authors.lastname: Combarnous
authors.forename: M
authors.initials: M
authors.lastname: Jankovic
authors.forename: S C
authors.initials: SC
authors.lastname: Maric
authors.forename: Z
authors.initials: Z
authors.lastname: Misulovin
authors.forename: M C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: T
authors.initials: T
authors.lastname: Feizi
mesh_terms: D000116:Acetylgalactosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002240:Carbohydrate Sequence; D002809:Chondroitin Sulfates / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D007986:Luteinizing Hormone / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D051379:Mice; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods
chemical_list: C402829:3-sulfated Lewis x; C086949:6'-sulfated sialyl Lewis x; D037102:Lectins; D037181:Lectins, C-Type; D007983:Lewis Blood Group Antigens; D016256:Lewis X Antigen; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009844:Oligosaccharides; D011134:Polysaccharides; D011509:Proteoglycans; D011956:Receptors, Cell Surface; D000080506:Sialyl Lewis X Antigen; C116504:sulfo-Lewis(a); C046736:N-acetylgalactosamine 6-sulfate; D003871:Dermatan Sulfate; C046735:N-acetylgalactosamine 4-sulfate; D007986:Luteinizing Hormone; D002809:Chondroitin Sulfates; D003545:Cysteine; D000116:Acetylgalactosamine