Progressive inactivation of cathepsin G and elastase released from activated neutrophils in vitro: lack of participation of the neutrophil alpha 1-proteinase inhibitor.
Addition of platelets to activated human polymorphonuclear neutrophils (PMNs) led to their aggregation and degranulation, with these responses decreasing as a function of the time interval between PMN activation and platelet addition. Thus, for a 15-second interval platelet aggregation and serotonin release reached 51.3% +/- 6.7% (n = 11) and 64.3% +/- 4.9% (n = 8), respectively, but after a 5-minute interval they were totally absent. This effect was correlated with the decrease in enzymatic activities of elastase (HLE) and cathepsin G (CAT-G) that were released on PMN activation and responsible for the activation of nearby platelets (r = 0.86 and 0.90 for CAT-G and HLE, respectively; p < 0.05). Because it has been recently shown that PMNs express an alpha 1-proteinase inhibitor (alpha 1-Pl) gene and secrete this antiproteinase at their surface, we investigated whether the PMN alpha 1-Pl could regulate the biologic activities of both proteinases. Although superoxide anions oxidize alpha 1-Pl and reduce its affinity for CAT-G and HLE, maneuvers aimed at modifying their concentrations did not modify the loss of CAT-G and HLE. In fact, the progressive decrease of the two proteinase enzymatic activities followed the same pattern whether PMNs were present or not. It is concluded that PMN alpha 1-Pl is not involved in the time-dependent inactivation of CAT-G and HLE released from activated PMNs.
Renesto
P
P
Unité de Pharmacologie Cellulaire, Unité associée IP/INSERM 285, Institut Pasteur, Paris, France.
Chignard
M
M
D001792:Blood Platelets / Q000502:physiology*; D056649:Cathepsin G; D002403:Cathepsins / Q000097:blood*; D002449:Cell Aggregation; D015550:Cell Degranulation; D006801:Humans; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology* / Q000502:physiology; D010196:Pancreatic Elastase / Q000097:blood*; D015539:Platelet Activation; D012697:Serine Endopeptidases; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D000515:alpha 1-Antitrypsin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase