N-acetylglucosamine 6-O-sulfotransferase-1 regulates expression of L-selectin ligands and lymphocyte homing.
Lymphocyte homing is initiated by the binding of L-selectin on lymphocytes to its ligands on high endothelial venules (HEV). Sialyl 6-sulfo Lewis X is a major capping group of L-selectin ligands. N-Acetylglucosamine (GlcNAc) 6-sulfation is essential for the ligand activity, and is catalyzed by GlcNAc 6-O-sulfotransferases (GlcNAc6STs) of which GlcNAc6ST-1 and GlcNAc6ST-2 are expressed in HEV. Here, we report that mice deficient in GlcNAc6ST-1 were impaired in the elaboration of sialyl 6-sulfo Lewis X in HEV and that an epitope of L-selectin ligands recognized by the MECA-79 anti-body was greatly reduced or abolished in the abluminal aspect of HEV. Lymphocyte homing to peripheral lymph nodes, mesenteric lymph nodes, and Peyer's patches was significantly reduced in GlcNAc6ST-1 null mice. These results demonstrate that GlcNAc6ST-1 is involved in lymphocyte homing in vivo, and indicate that GlcNAc6ST-1 and -2 play complementary roles. The importance of GlcNAc6ST-1 is particularly high-lighted by its involvement in lymphocyte homing to Peyer's patches where GlcNAc6ST-2 expression is undetectable.
Uchimura
Kenji
K
Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kadomatsu
Kenji
K
El-Fasakhany
Fathy M
FM
Singer
Mark S
MS
Izawa
Mineko
M
Kannagi
Reiji
R
Takeda
Naoki
N
Rosen
Steven D
SD
Muramatsu
Takashi
T
D000818:Animals; D015139:Blotting, Southern; D002384:Catalysis; D002448:Cell Adhesion; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000166:cytology; D000939:Epitopes / Q000737:chemistry; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D019041:L-Selectin / Q000378:metabolism*; D007962:Leukocytes / Q000378:metabolism; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009844:Oligosaccharides / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000080506:Sialyl Lewis X Antigen; D013234:Stem Cells / Q000378:metabolism; D015238:Sulfotransferases / Q000737:chemistry* / Q000378:metabolism; D000097811:Carbohydrate Sulfotransferases
D000939:Epitopes; D019041:L-Selectin; D008024:Ligands; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases