Abstract
The monoclonal antibody M-DC8 defines a major subset of human blood dendritic cells (DCs). Here we identify the M-DC8 structure as 6-sulfo LacNAc, a novel carbohydrate modification of the P selectin glycoprotein ligand 1 (PSGL-1). In contrast to previously described blood DCs, M-DC8+ DCs lack the cutaneous lymphocyte antigen (CLA) on PSGL-1 and fail to bind P and E selectin. Yet they express anaphylatoxin receptors (C5aR and C3aR) and the Fcgamma receptor III (CD16), which recruit cells to inflammatory sites. While sharing with DC1 the expression of myeloid markers and a potent capacity to prime T cells in vitro, M-DC8+ DCs produce far more TNF-alpha in response to the bacterial endotoxin lipopolysaccharide (LPS). Thus, 6-sulfo LacNAc-expressing DCs appear as a novel proinflammatory DC subset.
MeSH terms
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Adult
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Amino Sugars
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Animals
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Antibodies, Monoclonal / immunology
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Antigens, CD / analysis
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Blood Cells / immunology
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Carbohydrate Conformation
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Carbohydrate Sequence
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Cell Movement
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Dendritic Cells / classification
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Dendritic Cells / immunology*
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Dendritic Cells / transplantation
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E-Selectin / metabolism
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Epitopes / chemistry*
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Epitopes / immunology
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Glycosylation
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Humans
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Inflammation / immunology
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Lipopolysaccharides / immunology*
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Lipopolysaccharides / pharmacology
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Membrane Glycoproteins / chemistry*
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Membrane Glycoproteins / immunology
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Membrane Proteins*
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Mice
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Mice, SCID
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Molecular Sequence Data
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P-Selectin / metabolism
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Precipitin Tests
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Protein Processing, Post-Translational*
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Receptor, Anaphylatoxin C5a
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Receptors, Complement / analysis
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Receptors, IgG / analysis
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Transplantation, Heterologous
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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6-sulfo-LacNac
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Amino Sugars
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Antibodies, Monoclonal
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Antigens, CD
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E-Selectin
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Epitopes
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Lipopolysaccharides
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Membrane Glycoproteins
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Membrane Proteins
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P-Selectin
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P-selectin ligand protein
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Receptor, Anaphylatoxin C5a
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Receptors, Complement
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Receptors, IgG
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Tumor Necrosis Factor-alpha
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complement C3a receptor