1. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.
- Author
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Hidalgo A, Peired AJ, Wild M, Vestweber D, and Frenette PS
- Subjects
- Animals, Cell Adhesion, Hyaluronan Receptors analysis, Hyaluronan Receptors genetics, Leukocyte Rolling genetics, Ligands, Membrane Glycoproteins analysis, Membrane Glycoproteins genetics, Mice, Mice, Knockout, Neutrophils chemistry, Receptors, Fibroblast Growth Factor analysis, Receptors, Fibroblast Growth Factor genetics, Sialoglycoproteins analysis, Sialoglycoproteins genetics, E-Selectin immunology, Hyaluronan Receptors physiology, Membrane Glycoproteins physiology, Neutrophils immunology, Receptors, Fibroblast Growth Factor physiology, Sialoglycoproteins physiology
- Abstract
The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.
- Published
- 2007
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