Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment.
Lymphocyte homing is mediated by specific interaction between L-selectin on lymphocytes and the carbohydrate ligand 6-sulfo sialyl Lewis X on high endothelial venules. Here we generated mice lacking both core 1 extension and core 2 branching enzymes to assess the functions of O-glycan-borne L-selectin ligands in vivo. Mutant mice maintained robust lymphocyte homing, yet they lacked O-glycan L-selectin ligands. Biochemical analyses identified a class of N-glycans bearing the 6-sulfo sialyl Lewis X L-selectin ligand in high endothelial venules. These N-glycans supported the binding of L-selectin to high endothelial venules in vitro and contributed in vivo to O-glycan-independent lymphocyte homing in wild-type and mutant mice. Our results demonstrate the critical function of N-glycan-linked 6-sulfo sialyl Lewis X in L-selectin-dependent lymphocyte homing and recruitment.
Mitoma
Junya
J
Glycobiology Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, California 92037, USA.
Bao
Xingfeng
X
Petryanik
Bronislawa
B
Schaerli
Patrick
P
Gauguet
Jean-Marc
JM
Yu
Shin-Yi
SY
Kawashima
Hiroto
H
Saito
Hideo
H
Ohtsubo
Kazuaki
K
Marth
Jamey D
JD
Khoo
Kay-Hooi
KH
von Andrian
Ulrich H
UH
Lowe
John B
JB
Fukuda
Minoru
M
D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000276:immunology; D019041:L-Selectin / Q000276:immunology*; D016256:Lewis X Antigen / Q000031:analogs & derivatives; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D009844:Oligosaccharides / Q000276:immunology*; D011134:Polysaccharides / Q000276:immunology*; D000080506:Sialyl Lewis X Antigen / Q000031:analogs & derivatives
C086949:6'-sulfated sialyl Lewis x; D000954:Antigens, Surface; C069886:L-selectin counter-receptors; D016256:Lewis X Antigen; D008565:Membrane Proteins; D009844:Oligosaccharides; D011134:Polysaccharides; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin