Regulation of P-selectin binding to the neutrophil P-selectin counter-receptor P-selectin glycoprotein ligand-1 by neutrophil elastase and cathepsin G
| Autor: | Michael C. Berndt, Tracy McNally, Mariagrazia De Luca, Elizabeth E. Gardiner, Robert K. Andrews, Alan D. Michelson |
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| Rok vydání: | 2001 |
| Předmět: |
Cathepsin G
Neutrophils Immunology Molecular Sequence Data Granulocyte Biology Biochemistry chemistry.chemical_compound Cathepsin L1 medicine Humans Amino Acid Sequence Inflammation Membrane Glycoproteins integumentary system Elastase Serine Endopeptidases Metalloendopeptidases Cell Biology Hematology Neutrophil extracellular traps Molecular biology Cathepsins Autocrine Communication P-Selectin medicine.anatomical_structure chemistry Platelet Glycoprotein GPIb-IX Complex Neutrophil elastase Neutrophil degranulation biology.protein P-selectin glycoprotein ligand-1 Leukocyte Elastase Protein Binding |
| Zdroj: | Blood. 98(5) |
| ISSN: | 0006-4971 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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