EFFECT OF THE PROTEIN-KINASE-C INHIBITOR GF-109 203X ON ELASTASE RELEASE AND RESPIRATORY BURST OF HUMAN NEUTROPHILS

1. The effects of bisindolylmaleimide GF 109 203X, reported to be a po tent and highly selective inhibitor of protein kinase C (PKC), have be en investigated on some human neutrophil functions. 2. GF 109 203X pre vented O-2(-) production by NADPH-oxidase whatever the stimulus used f or polymorphonuclear neutrophil (PMN) activation: directs PKC activato rs like phorbol myristate acetate (PMA) and dioctanoylglycerol, calciu m ionophore (A23187), or receptor agonists like fMet-Leu-Phe (fMLP) an d opsonized zymosan. 3. The effect of GF 109 203X was also examined on elastase exocytosis by neutrophils. PMA-mediated elastase release was prevented by GF 109 203X. However, GF 109 203X had no effect on exocy tosis induced by A23187 and the effect of this compound on the fMLP re sponse changed according to its concentration. 4. These data suggest t hat PKC might be essential for stimulus-mediated O-2(-) production and also that PKC plays only a minor role in elastase secretion as compar ed to the role of the cytosolic calcium level. Copyright (C) 1996 Else vier Science Inc.