A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules.
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.
Uchimura
Kenji
K
Department of Anatomy, Program in Immunology, Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Gauguet
Jean-Marc
JM
Singer
Mark S
MS
Tsay
Durwin
D
Kannagi
Reiji
R
Muramatsu
Takashi
T
von Andrian
Ulrich H
UH
Rosen
Steven D
SD
D000117:Acetylglucosamine / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D000954:Antigens, Surface; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D019040:E-Selectin / Q000276:immunology; D004729:Endothelium, Lymphatic / Q000201:enzymology* / Q000276:immunology; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism*; D036904:Leukocyte Rolling; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008024:Ligands; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008565:Membrane Proteins / Q000172:deficiency*; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009844:Oligosaccharides / Q000172:deficiency*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives; D015238:Sulfotransferases / Q000172:deficiency* / Q000235:genetics; D000097811:Carbohydrate Sulfotransferases
D000117:Acetylglucosamine; D000954:Antigens, Surface; D019040:E-Selectin; D019041:L-Selectin; D016256:Lewis X Antigen; D008024:Ligands; D008565:Membrane Proteins; D009844:Oligosaccharides; D000080506:Sialyl Lewis X Antigen; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C086949:6'-sulfated sialyl Lewis x; C069886:L-selectin counter-receptors; C033137:N-acetylglucosamine-6-sulfate