title: DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis x residues.
abstract: Intercellular adhesion molecule-3 (ICAM-3) binds to the alpha(L)beta(2) integrin and mediates the contact between T cells and antigen-presenting cells. It has been suggested that dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN), a C-type lectin of macrophages and DCs, is an additional ligand of ICAM-3. So far, the glycan structure mediating the interaction of native ICAM-3 with DC-SIGN is undefined. Here, we demonstrate that native ICAM-3 from human peripheral leukocytes binds recombinant DC-SIGN, is recognized by monoclonal Lewis x antibodies, and specifically interacts with DC-SIGN on immature DCs. The presence of Lewis x residues on ICAM-3 was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy. Investigations on different peripheral blood cell populations revealed that only ICAM-3 from granulocytes bound DC-SIGN. Cotransfection studies demonstrated that fucosyltransferase (FUT) IX and, to a significantly lesser extent, FUT IV, but not FUTs III and VII, mediate the synthesis of Lewis x residues on ICAM-3. These findings indicate that FUT IX is the main FUT mediating the synthesis of Lewis x residues of ICAM-3 in cells of the myeloid lineage, and that these residues bind DC-SIGN. The results suggest that ICAM-3 assists in the interaction of granulocytes with DC-SIGN of DCs.
authors.affiliation: Institut für Klinische Chemie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20251 Hamburg, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bogoevska
authors.forename: Peter
authors.initials: P
authors.lastname: Nollau
authors.forename: Lothar
authors.initials: L
authors.lastname: Lucka
authors.forename: Detlef
authors.initials: D
authors.lastname: Grunow
authors.forename: Birgit
authors.initials: B
authors.lastname: Klampe
authors.forename: Liisa M
authors.initials: LM
authors.lastname: Uotila
authors.forename: Alexandra
authors.initials: A
authors.lastname: Samsen
authors.forename: Carl G
authors.initials: CG
authors.lastname: Gahmberg
authors.forename: Christoph
authors.initials: C
authors.lastname: Wagener
mesh_terms: D015703:Antigens, CD / Q000737:chemistry* / Q000302:isolation & purification; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000302:isolation & purification; D005647:Fucosyltransferases / Q000737:chemistry; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D037181:Lectins, C-Type / Q000737:chemistry*; D007962:Leukocytes / Q000276:immunology; D016256:Lewis X Antigen / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D005647:Fucosyltransferases; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C483616:ICAM3 protein, human; C519500:FUT9 protein, human