Alpha 2,3-sialyltransferase-IV is essential for L-selectin ligand function in inflammation

Eur J Immunol. 2006 Dec;36(12):3207-15. doi: 10.1002/eji.200636157.

Abstract

L-selectin belongs to the C-type lectin family of glycoproteins and is constitutively expressed on most leukocytes. L-selectin mediates leukocyte rolling in inflamed microvessels and high endothelial venules (HEV) via binding to specific carbohydrate structures on selectin ligands. Previous studies using sialidase treatment suggested a role of sialic acid residues in L-selectin-dependent rolling. To investigate the role of the alpha2,3-sialyltransferase (ST3Gal)-IV on L-selectin ligand activity in vivo, we studied leukocyte rolling in inflamed venules of the cremaster muscle and in Peyer's patch HEV of ST3Gal-IV-deficient mice and littermate control mice. In cremaster muscle venules with or without TNF-alpha treatment, L-selectin-dependent rolling was almost completely abolished in ST3Gal-IV(-/-) mice. In both models, L-selectin interacts with P-selectin glycoprotein ligand-1 (PSGL-1) presented by adherent leukocytes and leukocyte fragments, but not with endothelial L-selectin ligands. In contrast, L-selectin-dependent rolling in Peyer's patch HEV, which is mediated by unknown endothelial L-selectin ligands, was not impaired in the absence of ST3Gal-IV. Our in vivo data show that PSGL-1, the molecule responsible for L-selectin-mediated leukocyte interactions in inflammation, is dependent on ST3Gal-IV, while alpha2,3-sialylation by ST3Gal-IV is not necessary for L-selectin ligand activity on high endothelial cells of Peyer's patch HEV.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Immunoglobulin G / genetics
  • Immunoglobulin G / metabolism
  • Inflammation Mediators / physiology*
  • L-Selectin / genetics
  • L-Selectin / metabolism
  • L-Selectin / physiology*
  • Leukocytes / pathology
  • Ligands
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Chemokine / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sialyltransferases / deficiency
  • Sialyltransferases / genetics
  • Sialyltransferases / physiology*

Substances

  • Gr-1 protein, mouse
  • Immunoglobulin G
  • Inflammation Mediators
  • Ligands
  • Membrane Glycoproteins
  • P-selectin ligand protein
  • Receptors, Chemokine
  • Recombinant Fusion Proteins
  • L-Selectin
  • Sialyltransferases
  • beta-galactoside alpha-2,3-sialyltransferase