N-acetylglucosamine-6-O-sulfotransferases 1 and 2 cooperatively control lymphocyte homing through L-selectin ligand biosynthesis in high endothelial venules.
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.
Kawashima
Hiroto
H
Glycobiology Program, Cancer Research Center, The Burnham Institute, La Jolla, California 92037, USA.
Petryniak
Bronislawa
B
Hiraoka
Nobuyoshi
N
Mitoma
Junya
J
Huckaby
Valerie
V
Nakayama
Jun
J
Uchimura
Kenji
K
Kadomatsu
Kenji
K
Muramatsu
Takashi
T
Lowe
John B
JB
Fukuda
Minoru
M
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002465:Cell Movement; D003877:Dermatitis, Contact / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D004729:Endothelium, Lymphatic / Q000276:immunology / Q000378:metabolism*; D019041:L-Selectin / Q000378:metabolism*; D036904:Leukocyte Rolling; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008214:Lymphocytes / Q000201:enzymology / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D009077:Mucins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D009844:Oligosaccharides / Q000032:analysis / Q000096:biosynthesis*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism*; D000097811:Carbohydrate Sulfotransferases
D019041:L-Selectin; D016256:Lewis X Antigen; D008024:Ligands; D009077:Mucins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C086949:6'-sulfated sialyl Lewis x; C075185:sulfated glycoprotein p50