Related Experiment Videos
Sialyltransferase specificity in selectin ligand formation
Lesley G Ellies1, Markus Sperandio, Gregory H Underhill
1Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, and Howard Hughes Medical Institute, University of California, San Diego, La Jolla 92093, USA.
Blood
|October 24, 2002
Summary
ST3Gal sialyltransferases are crucial for selectin ligand formation in leukocyte trafficking. ST3Gal-IV plays a significant role in neutrophil selectin ligand synthesis and function during inflammation.
Area of Science:
- Glycobiology
- Immunology
- Cell Biology
Background:
- Selectin ligands, which are glycan structures, are key mediators of leukocyte trafficking and inflammation.
- At least six ST3Gal sialyltransferases (I-VI) are known to potentially contribute to selectin ligand formation.
- The in vivo roles and differential regulation of selectin function by these sialyltransferases remain largely unknown.
Purpose of the Study:
- To investigate the in vivo roles of ST3Gal-I, ST3Gal-II, ST3Gal-III, and ST3Gal-IV in selectin ligand formation.
- To determine if these sialyltransferases differentially regulate selectin function.
- To elucidate the specific contribution of ST3Gal-IV to neutrophil selectin ligand synthesis and function.
Main Methods:
- Generation and characterization of mice genetically deficient in ST3Gal-I, ST3Gal-II, ST3Gal-III, and ST3Gal-IV.
- Assessment of leukocytosis in single ST3Gal-deficient mice.
- In vitro analysis of neutrophil rolling on E- and P-selectins using Chinese hamster ovary (CHO) cells.
- In vivo evaluation of leukocyte rolling and velocity in a TNF-alpha-induced inflammation model.
Main Results:
- Single ST3Gal deficiencies did not result in leukocytosis, unlike severe selectin ligand formation defects.
- ST3Gal-IV was identified as the primary sialyltransferase involved in selectin ligand synthesis on neutrophils.
- In vitro neutrophil rolling on E- or P-selectins was reduced in ST3Gal-IV deficient neutrophils.
- In vivo, ST3Gal-IV deficiency led to decreased E-selectin-dependent leukocyte rolling and increased rolling velocity during TNF-alpha-induced inflammation, with no observed defect in P-selectin ligands.
Conclusions:
- Multiple ST3Gal sialyltransferases likely contribute to selectin ligand formation, as single deficiencies did not fully replicate neuraminidase treatment effects.
- ST3Gal-IV exhibits functional specificity and plays a substantial role in selectin ligand formation.
- These findings highlight the complex and specific roles of sialyltransferases in regulating leukocyte trafficking and inflammatory responses.