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Platelet activation by fMLP-stimulated polymorphonuclear leukocytes: the
activity of cathepsin G is not prevented by antiproteinases
V Evangelista, G Rajtar, G de Gaetano, JG White and C Cerletti
Giulio Bizzozero Laboratory of Platelet and Leukocyte Pharmacology,
Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy.
Human polymorphonuclear leukocytes (PMN) activated by fMLP (in the presence
of CaCl2, fibrinogen, and cytochalasin B) were able to induce aggregation,
cytoplasmic Ca2+ increase, and thromboxane A2 production in coincubated
autologousplatelets. Cell-free supernatants prepared from
n-formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated PMN were able
also to induce platelet activation. Antibodies against cathepsin G and
different serin protease inhibitors completely suppressed the activity of
PMN-derived supernatants, indicating that cathepsin G is the major platelet
activator released by PMN in our system. However, antiproteinases only
partially affected platelet activation induced by PMN in mixed cell
suspensions. Superoxide dismutase and catalase added to the cell suspension
did not affect platelet activation nor potentiated serin protease
inhibitors, making a role for short-lived oxygen radicals in our
experimental system unlikely. Electron microscopic observation of stirred
mixed cell suspensions preincubated for 2 minutes at 37 degrees C before
stimulation showed a close PMN- platelets contact without any morphologic
or biochemical event suggesting platelet activation. Preincubation of the
cells without stirring to minimize PMN-platelet interaction before
stimulation did not modify subsequent aggregation and platelet cytoplasmic
Ca2+ increase in control samples. However, in this condition trypsin
inhibitor from soybean completely prevented PMN-induced platelet
activation. In samples preincubated without stirring in the presence of the
antiproteinase, activated PMN stuck together but platelets preserved their
discoid shape and did not appear significantly activated. We propose that
membrane-to-membrane contact could create a microenvironment in which
cathepsin G, discharged from stimulated PMN on adherent platelets, is
protected from antiproteinases.
Volume 77,
Issue 11,
pp. 2379-2388,
06/01/1991
Copyright © 1991 by The American Society of Hematology
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