Abstract
Lymphocyte homing is mediated by specific interactions between L-selectin on lymphocytes and sulfated carbohydrates restricted to high endothelial venules in lymph nodes. Here we generated mice deficient in both N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2 and found that mutant mice had approximately 75% less homing of lymphocytes to the peripheral lymph nodes than did wild-type mice. Consequently, these mice had lower contact hypersensitivity responses than those of wild-type mice. Carbohydrate structural analysis showed that 6-sulfo sialyl Lewis X, a dominant ligand for L-selectin, was almost completely absent from the high endothelial venules of these mutant mice, whereas the amount of unsulfated sialyl Lewis X was much greater. These results demonstrate the essential function of GlcNAc6ST-1 and GlcNAc6ST-2 in L-selectin ligand biosynthesis in high endothelial venules and their importance in immune surveillance.
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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Animals
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Carbohydrate Conformation
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Carbohydrate Sequence
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Carbohydrate Sulfotransferases
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Cell Movement
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Dermatitis, Contact / enzymology
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Dermatitis, Contact / genetics
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Dermatitis, Contact / immunology
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Endothelium, Lymphatic / immunology
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Endothelium, Lymphatic / metabolism*
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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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Lymphocytes / enzymology
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Lymphocytes / immunology*
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Mice
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Mice, Knockout
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Mucins / chemistry
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Mucins / metabolism
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Mutation
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Oligosaccharides / analysis
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Oligosaccharides / biosynthesis*
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Sialyl Lewis X Antigen / analogs & derivatives
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Substrate Specificity
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Sulfotransferases / genetics
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Sulfotransferases / metabolism*
Substances
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6'-sulfated sialyl Lewis x
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Lewis X Antigen
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Ligands
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Mucins
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Oligosaccharides
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Sialyl Lewis X Antigen
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L-Selectin
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sulfated glycoprotein p50
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Sulfotransferases