Activation of human platelets by C5a-stimulated neutrophils: a role for cathepsin G
| Autor: | M Chignard, P Laurent, P Renesto, S Bassot, P Ferrer-Lopez, M Schattner |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Blood Platelets
Serotonin Cathepsin G Physiology Neutrophils Molecular Sequence Data Complement C5a Biology In Vitro Techniques chemistry.chemical_compound Cathepsin L1 Humans Platelet Protease Inhibitors Platelet activation Amino Acid Sequence Platelet Activating Factor Cathepsin S Cathepsin Platelet-activating factor Aspirin Pancreatic Elastase Serine Endopeptidases Cell Biology Azepines N-Formylmethionine leucyl-phenylalanine Triazoles Platelet Activation Cathepsins Recombinant Proteins N-Formylmethionine Leucyl-Phenylalanine Kinetics chemistry Biochemistry Oligopeptides |
| Zdroj: | The American journal of physiology. 258(6 Pt 1) |
| ISSN: | 0002-9513 |
| Popis: | Human platelets can be stimulated by recombinant human fifth component of complement (rhC5a) in the presence of human neutrophils. After challenge with N-formyl-Met-Leu-Phe or rhC5a, concentrated neutrophils release cathepsin G into the supernatant. The concentrations of cathepsin G recovered by titration of the enzymatic activity correlate with the capability of these supernatants to induce platelet stimulation as measured by serotonin release. Cathepsin G purified from neutrophil granules triggered platelet aggregation and serotonin release independent of arachidonic acid metabolites and platelet-activating factor formation. A concentration of 100 nM of cathepsin G, which was reached in the surrounding space of activated neutrophils, induced a 50% platelet stimulation. Three distinct antiproteinases were tested against cathepsin G-induced platelet activation. Z-Gly-Leu-Phe-CH2Cl, a specific inhibitor of cathepsin G enzymatic activity, proved to be nonspecific in our biological system. By contrast, alpha 1-antichymotrypsin and alpha 1-antitrypsin displayed specific activities. The physiological specific inhibitor of cathepsin G, alpha 1-antichymotrypsin, was the most potent and was used in the rhC5a-induced neutrophils-mediated platelet activation. A complete inhibition was achieved, showing that release of cathepsin G from neutrophils accounts for platelet activation. Such a chain of events involving C5a, neutrophils, cathepsin G, and platelets may be of relevance in certain inflammatory states, particularly the adult respiratory distress syndrome. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|