Leukocyte ligands for endothelial selectins: specialized glycoconjugates that mediate rolling and signaling under flow

Blood. 2011 Dec 22;118(26):6743-51. doi: 10.1182/blood-2011-07-343566. Epub 2011 Oct 20.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • E-Selectin / immunology*
  • E-Selectin / metabolism
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism
  • Glycoconjugates / immunology
  • Glycoconjugates / metabolism
  • Humans
  • Hyaluronan Receptors / immunology*
  • Hyaluronan Receptors / metabolism
  • Leukocyte Rolling / immunology
  • Leukocytes / immunology*
  • Leukocytes / metabolism
  • Ligands
  • Membrane Glycoproteins / immunology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • P-Selectin / immunology*
  • P-Selectin / metabolism
  • Receptors, Fibroblast Growth Factor / immunology*
  • Receptors, Fibroblast Growth Factor / metabolism
  • Sialoglycoproteins / immunology*
  • Sialoglycoproteins / metabolism
  • Signal Transduction / immunology
  • Stress, Mechanical

Substances

  • CD44 protein, human
  • E-Selectin
  • Glycoconjugates
  • Hyaluronan Receptors
  • Ligands
  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Receptors, Fibroblast Growth Factor
  • Sialoglycoproteins
  • cysteine-rich fibroblast growth factor receptor