Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.
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.
Hidalgo
Andrés
A
Department of Medicine and Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029.
Peired
Anna J
AJ
Department of Medicine and Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029.
Wild
Martin
M
Department of Cell Biology, Max-Planck-Institute of Molecular Biomedicine, Muenster, Germany.
Vestweber
Dietmar
D
Department of Cell Biology, Max-Planck-Institute of Molecular Biomedicine, Muenster, Germany.
Frenette
Paul S
PS
Department of Medicine and Immunobiology Center, Mount Sinai School of Medicine, New York, NY 10029.
D000818:Animals; D002448:Cell Adhesion; D019040:E-Selectin / Q000276:immunology*; D018960:Hyaluronan Receptors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D036904:Leukocyte Rolling / Q000235:genetics; D008024:Ligands; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000737:chemistry / Q000276:immunology*; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
D019040:E-Selectin; D018960:Hyaluronan Receptors; D008024:Ligands; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor