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Enhancement of cathepsin G-induced platelet activation by leukocyte
elastase: consequence for the neutrophil-mediated platelet activation
P Renesto and M Chignard
Unite de Pharmacologie Cellulaire, Unite Associee Institut Pasteur/INSERM
285, Institut Pasteur, Paris, France.
We have focused our interest on the platelet-activating properties of two
polymorphonuclear neutrophil (PMN)-derived proteinases, namely elastase
(HLE) and cathepsin G (Cat.G). First of all, we observed that whereas HLE
was unable to trigger platelet activation by itself, it enhanced platelet
activation induced by Cat.G when both proteinases were added
simultaneously. It has been recently described that, upon stimulation, PMN
released Cat.G, which in turn activated surrounding platelets. Thus, we
looked for a combined effect of Cat.G and HLE during this cell-to-cell
interaction. When PMN (5 x 10(6)/mL) were stimulated by 0.5 mumol/L
N-formyl-Met-Leu-Phe, they released 237.9 +/- 49.1 nmol/L Cat.G and 381.7
+/- 28.0 nmol/L HLE. Such a concentration of purified Cat.G (240 nmol/L)
induced only a moderate platelet activation when added to a PMN-platelet
mixture. However, when Cat.G (240 nmol/L) and HLE (380 nmol/L) were added
together, the resulting platelet activation was strictly comparable to that
corresponding to the addition of N-formyl-Met-Leu-Phe (P > .05) in terms
of aggregation, dense and alpha granule secretion, and thromboxane B2
production. In fact, Elafin, a specific HLE inhibitor, when added to the
PMN-platelet cooperation system triggered by N-formyl-Met-Leu-Phe,
prevented platelet activation within the same range of concentrations as
for inhibition of HLE activity. In conclusion, we now show that not only
Cat.G, but also HLE is involved in the PMN-mediated platelet activation.
Volume 82,
Issue 1,
pp. 139-144,
07/01/1993
Copyright © 1993 by The American Society of Hematology

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