Inhibition by human leukocyte elastase of neutrophil-mediated platelet activation.
When human polymorphonuclear neutrophils and platelets were incubated with human leukocyte elastase before N-formyl-Met-Leu-Phe (FMLP) challenge, a time- and concentration-dependent inhibition of the resulting platelet activation was observed. Thus, when the mixed cell suspension was preincubated for 6 min with 1 microM elastase before stimulation of neutrophils with 0.5 microM FMLP, resulting aggregations and serotonin releases were respectively only 4.4 +/- 4.1% (n = 4) and 1.6 +/- 2.4% (n = 4) as compared to 41.6 +/- 5.2% (n = 9) and 71.3 +/- 16.0 (n = 9) for controls. A direct inhibitory action of elastase on neutrophil activation was ruled out, as well as a breakdown of cathepsin G, a mediator involved in neutrophil-mediated platelet activation. In fact, we demonstrated that the target for the inhibitory effect of elastase in such a cell-to-cell cooperation system was the platelet. This phenomenon is likely to play a role under in vivo conditions in pathologies in which a significant granulocytic proteolytic activity has been detected in the plasma.
Renesto
P
P
Unité de Pharmacologie Cellulaire, Unité Associée IP/INSERM no. 285, Institut Pasteur, Paris, France.
Balloy
V
V
Chignard
M
M
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D056649:Cathepsin G; D002403:Cathepsins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019272:Leukocyte Elastase; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D010196:Pancreatic Elastase / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D012697:Serine Endopeptidases; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase