Abstract
The interaction of L-selectin on lymphocytes with sulfated ligands on high endothelial venules leads to rolling and is critical for recruitment of lymphocytes into peripheral lymph nodes. Peripheral node addressin represents a class of L-selectin ligands recognized by the function-blocking monoclonal antibody MECA-79. Its epitope overlaps with sialyl 6-sulfo Lewis X, an L-selectin recognition determinant. Here, mice lacking two N-acetylglucosamine-6-O-sulfotransferases (GlcNAc6ST-1 and GlcNAc6ST-2) demonstrated elimination of both peripheral node addressin and sialyl 6-sulfo Lewis X in high endothelial venules, considerably reduced lymphocyte homing to peripheral lymph nodes and reduced sticking of lymphocytes along high endothelial venules. Our results establish an essential function for the sulfotransferases in L-selectin ligand synthesis and may have relevance for therapy of inflammatory diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Acetylglucosamine / analogs & derivatives
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Acetylglucosamine / metabolism
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Animals
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Antigens, Surface
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B-Lymphocytes / enzymology
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B-Lymphocytes / immunology*
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Carbohydrate Sulfotransferases
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E-Selectin / immunology
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Endothelium, Lymphatic / enzymology*
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Endothelium, Lymphatic / immunology
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L-Selectin / immunology
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L-Selectin / metabolism*
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Leukocyte Rolling*
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Lewis X Antigen / analogs & derivatives
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Ligands
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Membrane Proteins / deficiency*
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Mice
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Mice, Knockout
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Mutation
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Oligosaccharides / deficiency*
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Sialyl Lewis X Antigen / analogs & derivatives
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Sulfotransferases / deficiency*
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Sulfotransferases / genetics
Substances
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6'-sulfated sialyl Lewis x
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Antigens, Surface
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E-Selectin
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L-selectin counter-receptors
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Lewis X Antigen
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Ligands
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Membrane Proteins
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Oligosaccharides
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Sialyl Lewis X Antigen
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N-acetylglucosamine-6-sulfate
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L-Selectin
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Sulfotransferases
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Acetylglucosamine