Impaired selectin-ligand biosynthesis and reduced inflammatory responses in beta-1,4-galactosyltransferase-I-deficient mice

Blood. 2003 Sep 1;102(5):1678-85. doi: 10.1182/blood-2003-03-0836. Epub 2003 Apr 24.

Abstract

Selectins recognize ligands containing carbohydrate chains such as sialyl Lewis x (sLex) that are mainly presented at the terminus of N-acetyl lactosamine repeats on core 2 O-glycans. Several glycosyltransferases act successively to extend the N-acetyl lactosamine repeats and to synthesize sLex, and beta-1,4-galactosyltransferase (beta4GalT) plays a key role in these processes. Recently isolated 6 beta4GalT genes are candidates, but their individual roles, including those in selectin-ligand biosynthesis, remain to be elucidated. More than 80% of the core 2 O-glycans on the leukocyte membrane glycoproteins of beta4GalT-I-deficient mice lacked galactose residues in beta-1,4 linkage, and soluble P-selectin binding to neutrophils and monocytes of these mice was significantly reduced, indicating an impairment of selectin-ligand biosynthesis. beta4GalT-I-deficient mice exhibited blood leukocytosis but normal lymphocyte homing to peripheral lymph nodes. Acute and chronic inflammatory responses, including the contact hypersensitivity (CHS) and delayed-type hypersensitivity (DTH) responses, were suppressed, and neutrophil infiltration into inflammatory sites was largely reduced in these mice. Our results demonstrate that beta4GalT-I is a major galactosyltransferase responsible for selectin-ligand biosynthesis and that inflammatory responses of beta4GalT-I-deficient mice are impaired because of the defect in selectin-ligand biosynthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Chronic Disease
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / metabolism*
  • Galactosyltransferases / genetics*
  • Galactosyltransferases / immunology
  • Galactosyltransferases / metabolism
  • Hypersensitivity, Delayed / immunology
  • Hypersensitivity, Delayed / metabolism*
  • Leukocytosis / physiopathology
  • Ligands
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Monocytes / enzymology*
  • Monocytes / immunology
  • Neutrophils / enzymology*
  • Neutrophils / immunology
  • Polysaccharides / biosynthesis
  • Polysaccharides / immunology
  • Protein Binding / immunology
  • Selectins / metabolism*

Substances

  • Ligands
  • Polysaccharides
  • Selectins
  • Galactosyltransferases
  • beta-1,4-galactosyltransferase I