CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis x residues.
The CEA-related cell adhesion molecule 1, CEACAM1, is a glycoprotein expressed on the surface of human granulocytes and lymphocytes, endothelia, and many epithelia. CEACAM1 is involved in the regulation of important biological processes, such as tumor growth, angiogenesis, and modulation of the immune response. CEACAM1, a member of the immunoglobulin superfamily carries several Lewis x (Lex) structures as we recently demonstrated by mass spectrometry of native CEACAM1 from human granulocytes. Since Lex residues of pathogens bind to the C-type lectin dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) expressed on human DCs, we hypothesized that Lex glycans of CEACAM1 are recognized by DC-SIGN. Here, we demonstrate that CEACAM1, the major carrier of Lex residues in human granulocytes, is specifically recognized by DC-SIGN via Lex residues mediating the internalization of CEACAM1 into immature DCs. Expression studies with CEACAM1 in combination with different fucosyltransferases (FUTs) revealed that FUTIX plays a key role in the synthesis of Lex groups of CEACAM1. As Lex groups on CEACAM1 are selectively attached and specifically interact with DC-SIGN, our findings suggest that CEACAM1 participates in immune regulation in physiological conditions and in pathological conditions, such as inflammation, autoimmune disease, and cancer.
Bogoevska
Valentina
V
Institute of Clinical Chemistry, University Clinic Hamburg-Eppendorf, Martinistr, 52, 20251 Hamburg, Germany.
Horst
Andrea
A
Klampe
Birgit
B
Lucka
Lothar
L
Wagener
Christoph
C
Nollau
Peter
P
D000818:Animals; D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D002454:Cell Differentiation; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism*; D005643:Fucose / Q000737:chemistry / Q000378:metabolism*; D005647:Fucosyltransferases / Q000378:metabolism*; D015870:Gene Expression; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D016256:Lewis X Antigen / Q000378:metabolism*; D008024:Ligands; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D005643:Fucose; D005647:Fucosyltransferases; D037181:Lectins, C-Type; D016256:Lewis X Antigen; D008024:Ligands; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin; C069847:CD66 antigens