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Glycobiology Advance Access originally published online on December 4, 2006
Glycobiology 2007 17(3):324-333; doi:10.1093/glycob/cwl073
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© 2006 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis x residues

Valentina Bogoevska2, Peter Nollau2, Lothar Lucka3, Detlef Grunow3, Birgit Klampe2, Liisa M. Uotila4, Alexandra Samsen2, Carl G. Gahmberg4 and Christoph Wagener1,2

2 Institut für Klinische Chemie, Universitätsklinikum Hamburg-Eppendorf, Martinistraße 52, D-20251 Hamburg, Germany
3 Institut für Biochemie und Molekularbiologie, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Arnimallee 22, D-14195 Berlin, Germany
4 Division of Biochemistry, Department of Biological and Environmental Sciences, University of Helsinki, FIN-00014 Helsinki, Finland

1 To whom correspondence should be addressed; Tel: 49 40 42803 2981; Fax: 49 40 42803 4621; e-mail: wagener{at}uke.uni-hamburg.de

Received on October 11, 2006; revised on November 20, 2006; accepted on November 21, 2006

Intercellular adhesion molecule-3 (ICAM-3) binds to the {alpha}Lß2 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.

Key words: carcinoembryonic antigen-related cell adhesion molecule-1 / dendritic cell-specific ICAM-3 grabbing nonintegrin / fucosyltransferases / intercellular adhesion molecule-3 / Lewis x


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