Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow.
Reversible interactions of glycoconjugates on leukocytes with P- and E-selectin on endothelial cells mediate tethering and rolling of leukocytes in inflamed vascular beds, the first step in their recruitment to sites of injury. Although selectin ligands on hematopoietic precursors have been identified, here we review evidence that PSGL-1, CD44, and ESL-1 on mature leukocytes are physiologic glycoprotein ligands for endothelial selectins. Each ligand has specialized adhesive functions during tethering and rolling. Furthermore, PSGL-1 and CD44 induce signals that activate the β2 integrin LFA-1 and promote slow rolling, whereas ESL-1 induces signals that activate the β2 integrin Mac-1 in adherent neutrophils. We also review evidence for glycolipids, CD43, L-selectin, and other glycoconjugates as potential physiologic ligands for endothelial selectins on neutrophils or lymphocytes. Although the physiologic characterization of these ligands has been obtained in mice, we also note reported similarities and differences with human selectin ligands.
Department of Anesthesiology and Intensive Care Medicine, University of Münster and Max-Planck Institute, Germany.
Alexander
A
Zarbock
Klaus
K
Ley
Rodger P
RP
McEver
Andrés
A
Hidalgo
D000818:Animals; D019040:E-Selectin / Q000276:immunology* / Q000378:metabolism; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism; D006001:Glycoconjugates / Q000276:immunology / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000276:immunology* / Q000378:metabolism; D036904:Leukocyte Rolling / Q000276:immunology; D007962:Leukocytes / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D019007:P-Selectin / Q000276:immunology* / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000276:immunology* / Q000378:metabolism; D012795:Sialoglycoproteins / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013314:Stress, Mechanical
C497483:CD44 protein, human; D019040:E-Selectin; D006001:Glycoconjugates; D018960:Hyaluronan Receptors; D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor