Combined activation of platelets by cathepsin G and platelet activating factor, two neutrophil-derived agonists.
In this paper we have studied the combined effects on platelet activation, of two polymorphonuclear neutrophil (PMN)-derived agonists, namely platelet-activating factor (PAF) and cathepsin G (Cat.G), used at threshold concentrations. Our results showed that the order of agonist addition was a determinant factor since the addition of Cat.G prior to PAF induced a full platelet activation while the reverse combination had no effects. The successive challenge of platelets by Cat.G and then PAF induced a strong aggregation accompanied by an enhancement of alpha and dense granule secretion. The observed phenomenon was also dependent on the time interval between agonist addition. It was significant at 30 s (P less than 0.05) and plateaued over 1-2 min. Platelet activation resulting from the combination Cat.G-PAF can be described as a function of PAF concentrations, the synergism being significant between 10 nM and 1 microM. The mechanism by which Cat.G primes platelets remains to be elucidated. However, some points have been examined and have led us to conclude that an increase in expression and/or affinity of PAF receptors, [Ca2+]i movements, protein kinase C activation and phospholipase A2 pathway are not involved. Whatever the biochemical mechanism underlying this synergism which involved PMN and platelets, it may constitute a link between the inflammatory and haemostatic processes in response to tissue damage.
Renesto
P
P
Unité de Pharmacologie Cellulaire, Institut Pasteur, Paris, France.
Kadiri
C
C
Chignard
M
M
D056649:Cathepsin G; D002403:Cathepsins / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000502:physiology*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D012697:Serine Endopeptidases
D010972:Platelet Activating Factor; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G