Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation.

Abstract

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.

• Authors: L G Ellies, S Tsuboi, B Petryniak, J B Lowe, M Fukuda, J D Marth
• Journal: Immunity (Immunity) Vol. 9 Issue 6 Pg. 881-90 (Dec 1998) ISSN: 1074-7613 [Print] United States
• PMID: 9881978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Ligands
• Oligosaccharides
• Polysaccharides
• L-Selectin
• Galactosyltransferases
• glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase

Topics

• Animals
• Cell Movement
• Galactosyltransferases (genetics, metabolism, physiology)
• Gene Targeting
• L-Selectin (biosynthesis)
• Ligands
• Mice
• Mice, Inbred BALB C
• Mutagenesis
• Neutrophils (immunology, physiology)
• Oligosaccharides (metabolism)
• Polysaccharides (metabolism)