Research Highlights
Leukocytes: Roll over with ST3Gal-IV
Functional Glycomics (14 December 2006) | doi:10.1038/fg.2006.5Standfirst
P-selectin glycoprotein ligand-1 (PSGL-1), which enables rolling of leukocytes at sites of inflammation by interaction with the various selectins, is sialylated by 
2,3-sialyltransferase-IV (ST3Gal-IV).
Copyright © 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Leukocyte rolling during inflammation involves repeated bond-making and bond-breaking between a group of calcium-dependent lectins — the selectins — and specific carbohydrate structures, both of which are found on leukocytes and endothelial cells. P-, E- and L-selectin bind carbohydrates on PSGL-1, among them a sialic acid molecule 2,3-linked to galactose. When leukocytes become adherent to endothelial cells of inflamed blood vessels (venules), leukocyte expressed PSGL-1 interacts with L-selectin presented on leukocytes rolling over them; the presence of P-selectin, on the other hand, enables leukocyte rolling directly over inflamed endothelial cells. Sperandio and colleagues report in the European Journal of Immunology that they have now identified the transferase which forms the 2,3-sialylated galactose structure on PSGL-1 relevant for L-selectin dependent rolling during inflammation in vivo.
Previous studies indicated that ST3Gal-IV plays an important role in blood physiology processes such as hemostasis. Therefore, Sperandio et al. have now investigated leukocyte rolling in muscle venules of mice lacking ST3Gal-IV-/-. The authors induced inflammation in both normal and ST3Gal-IV-/- mice by trauma and by exposure to tumor necrosis factor-. By inhibiting P- and E-selectin, L-selectin-dependent rolling was observed in wild type mice but not in ST3Gal-IV-/- mice suggesting that the L-selectin ligand function exerted by PSGL-1 is dependent on ST3Gal-IV. In addition, immunodetection by FACS analysis revealed that leukocytes of ST3Gal-IV-/- mice did not bind to a L-selectin-immunoglobulin chimeric protein.
These results demonstrate that one of the physiological functions of ST3Gal-IV is the sialylation of PSGL-1. Taken together, this study significantly expands our understanding of the physiological functions of the six known mammalian transferases that synthesize 2,3-sialylated galactose structures.
Original paper:
- Sperandio M et al. 2,3-Sialyltransferase-IV is essential for L-selectin ligand function in inflammation. Eur.J.Immunol. 363 207–215 (2006). http://www3.interscience.wiley.com/cgi-bin/abstract/113468483/ABSTRACT doi: 10.1002/eji.200636157