Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands

Won Ho Yang, Claudia Nussbaum, Prabhjit K. Grewal, Jamey D. Marth, Markus Sperandio

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Binding of selectins to their glycan ligands is a prerequisite for successful leukocyte trafficking. During synthesis and transport through the secretory pathway, selectin ligands are constructed with the participation of one or more sialyltransferases of the ST3Gal subfamily. Previous studies established that ST3Gal-IV only partially contributes to selectin ligand formation, indicating that other ST3Gal-sialyltransferases are involved. By generating and analyzing St3gal6-null mice and St3gal4/St3gal6 double-deficient mice, in the present study, we found that binding of E- and P-selectin to neutrophils and L-selectin binding to lymph node high endothelial venules is reduced in the absence of ST3Gal-VI and to a greater extent in double-deficient mice. In an ex vivo flow chamber assay, P- and E-selectin-dependent leukocyte rolling was mildly reduced in St3gal6-null mice and more severely in double-deficient mice. In inflamed cremaster muscle venules of St3gal6-null mice, we found impaired P-selectin-dependent, but not E-selectin-dependent leukocyte rolling, whereas in double-deficient mice, E-selectin-dependent rolling was almost completely absent. Furthermore, neutrophil recruitment into the inflamed peritoneal cavity and lymphocyte homing to secondary lymphoid organs were impaired in St3gal6-null mice and more severely in double-deficient mice. The results of the present study demonstrate the coordinated participation of both ST3Gal-VI and ST3Gal-IV in the synthesis of functional selectin ligands.

Original languageEnglish
Pages (from-to)1015-1026
Number of pages12
JournalBlood
Volume120
Issue number5
DOIs
Publication statusPublished - 2012 Aug 2

Fingerprint

beta-galactoside alpha-2,3-sialyltransferase
Sialyltransferases
Selectins
E-Selectin
P-Selectin
Ligands
L-Selectin
Leukocyte Rolling
Lymphocytes
Venules
Polysaccharides
Muscle
Assays
Abdominal Muscles
Neutrophil Infiltration
Secretory Pathway
Peritoneal Cavity

All Science Journal Classification (ASJC) codes

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Yang, Won Ho ; Nussbaum, Claudia ; Grewal, Prabhjit K. ; Marth, Jamey D. ; Sperandio, Markus. / Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands. In: Blood. 2012 ; Vol. 120, No. 5. pp. 1015-1026.
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Coordinated roles of ST3Gal-VI and ST3Gal-IV sialyltransferases in the synthesis of selectin ligands. / Yang, Won Ho; Nussbaum, Claudia; Grewal, Prabhjit K.; Marth, Jamey D.; Sperandio, Markus.

In: Blood, Vol. 120, No. 5, 02.08.2012, p. 1015-1026.

Research output: Contribution to journalArticle

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AB - Binding of selectins to their glycan ligands is a prerequisite for successful leukocyte trafficking. During synthesis and transport through the secretory pathway, selectin ligands are constructed with the participation of one or more sialyltransferases of the ST3Gal subfamily. Previous studies established that ST3Gal-IV only partially contributes to selectin ligand formation, indicating that other ST3Gal-sialyltransferases are involved. By generating and analyzing St3gal6-null mice and St3gal4/St3gal6 double-deficient mice, in the present study, we found that binding of E- and P-selectin to neutrophils and L-selectin binding to lymph node high endothelial venules is reduced in the absence of ST3Gal-VI and to a greater extent in double-deficient mice. In an ex vivo flow chamber assay, P- and E-selectin-dependent leukocyte rolling was mildly reduced in St3gal6-null mice and more severely in double-deficient mice. In inflamed cremaster muscle venules of St3gal6-null mice, we found impaired P-selectin-dependent, but not E-selectin-dependent leukocyte rolling, whereas in double-deficient mice, E-selectin-dependent rolling was almost completely absent. Furthermore, neutrophil recruitment into the inflamed peritoneal cavity and lymphocyte homing to secondary lymphoid organs were impaired in St3gal6-null mice and more severely in double-deficient mice. The results of the present study demonstrate the coordinated participation of both ST3Gal-VI and ST3Gal-IV in the synthesis of functional selectin ligands.

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