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 potent and highly selective inhibitor of protein kinase C (PKC), have been investigated on some human neutrophil functions. 2. GF 109 203X prevented O.2- production by NADPH-oxidase whatever the stimulus used for polymorphonuclear neutrophil (PMN) activation: directs PKC activators like phorbol myristate acetate (PMA) and dioctanoylglycerol, calcium ionophore (A23187), or receptor agonists like fMet-Leu-Phe (fMLP) and opsonized zymosan. 3. The effect of GF 109 203X was also examined on elastase exocytosis by neutrophils. PMA-mediated release was prevented by GF 109 203X. However, GF 109 203X had no effect on exocytosis induced by A23187 and the effect of this compound on the fMLP response changed according to its concentration. 4. These data suggest that PKC might be essential for stimulus-mediated O.2- production and also that PKC plays only a minor role in elastase secretion as compared to the role of the cytosolic calcium level.
Cabanis
A
A
Faculté des Sciences Pharmaceutiques et Biologiques, Laboratoire de Pharmacologie, Lille, France.
Gressier
B
B
Brunet
C
C
Dine
T
T
Luyckx
M
M
Cazin
M
M
Cazin
J C
JC
D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D019272:Leukocyte Elastase / Q000097:blood*; D008301:Maleimides / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D016897:Respiratory Burst / Q000187:drug effects*; D013481:Superoxides / Q000097:blood; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D013481:Superoxides; D000001:Calcimycin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D007770:L-Lactate Dehydrogenase; D011493:Protein Kinase C; D019272:Leukocyte Elastase; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium