Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation.
Mammalian serine/threonine-linked oligosaccharides (O-glycans) are commonly synthesized with the Golgi enzyme core 2 beta-1,6-N-acetylglucosaminyltransferase (C2 GlcNAcT). Core 2 O-glycans have been hypothesized to be essential for mucin production and selectin ligand biosynthesis. We report that mice lacking C2 GlcNAcT exhibit a restricted phenotype with neutrophilia and a partial deficiency of selectin ligands. Loss of core 2 oligosaccharides reduces neutrophil rolling on substrata bearing E-, L-, and P-selectins and neutrophil recruitment to sites of inflammation. However, the diminished presence of L-selectin ligands on lymph node high endothelial venules does not affect lymphocyte homing. These studies indicate that core 2 oligosaccharide biosynthesis segregates the physiologic roles of selectins and reveal a function for the C2 GlcNAcT in myeloid homeostasis and inflammation.
Ellies
L G
LG
Howard Hughes Medical Institute, Division of Cellular and Molecular Medicine, University of California San Diego, La Jolla 92093, USA.
Tsuboi
S
S
Petryniak
B
B
Lowe
J B
JB
Fukuda
M
M
Marth
J D
JD
D000818:Animals; D002465:Cell Movement; D005700:Galactosyltransferases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018390:Gene Targeting; D019041:L-Selectin / Q000096:biosynthesis; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D016296:Mutagenesis; D009504:Neutrophils / Q000276:immunology / Q000502:physiology*; D009844:Oligosaccharides / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism
D008024:Ligands; D009844:Oligosaccharides; D011134:Polysaccharides; D019041:L-Selectin; D005700:Galactosyltransferases; C076385:glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase