Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G

Blood. 2001 Sep 1;98(5):1440-7. doi: 10.1182/blood.v98.5.1440.


In the inflammatory response, leukocyte rolling before adhesion and transmigration through the blood vessel wall is mediated by specific cell surface adhesion receptors. Neutrophil rolling involves the interaction of P-selectin expressed on activated endothelium and its counter-receptor on neutrophils, P-selectin glycoprotein ligand-1 (PSGL-1). Here, it is reported that P-selectin binding to neutrophils is lost under conditions that cause the release of proteinases from neutrophil primary granules. Treatment of neutrophils with the purified neutrophil granule proteinases, cathepsin G and elastase, rapidly abolished their capacity to bind P-selectin. This inactivation corresponded to loss of the N-terminal domain of PSGL-1, as assessed by Western blot analysis. A loss of intact PSGL-1 protein from the surfaces of neutrophils after the induction of degranulation was also detected by Western blot analysis. Cathepsin G initially cleaved near the PSGL-1 N-terminus, whereas neutrophil elastase predominantly cleaved at a more C-terminal site within the protein mucin core. Consistent with this, cathepsin G cleaved a synthetic peptide based on the PSGL-1 N-terminus between Tyr-7/Leu-8. Under conditions producing neutrophil degranulation in incubations containing mixtures of platelets and neutrophils, the loss of PSGL-1, but not P-selectin, from platelet-neutrophil lysates was detected. Cathepsin G- or neutrophil elastase-mediated PSGL-1 proteolysis may constitute a potential autocrine mechanism for down-regulation of neutrophil adhesion to P-selectin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autocrine Communication
  • Cathepsin G
  • Cathepsins / physiology*
  • Humans
  • Inflammation / metabolism
  • Leukocyte Elastase / physiology*
  • Membrane Glycoproteins / metabolism*
  • Metalloendopeptidases / pharmacology
  • Molecular Sequence Data
  • Neutrophils / drug effects
  • Neutrophils / enzymology*
  • Neutrophils / metabolism
  • P-Selectin / metabolism*
  • Platelet Glycoprotein GPIb-IX Complex / chemistry
  • Protein Binding
  • Serine Endopeptidases


  • Membrane Glycoproteins
  • P-Selectin
  • P-selectin ligand protein
  • Platelet Glycoprotein GPIb-IX Complex
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Leukocyte Elastase
  • Metalloendopeptidases
  • mocarhagin