Role of protein kinase C in neutrophil survival enhanced by granulocyte colony-stimulating factor.
Recombinant human granulocyte colony-stimulating factor (rhG-CSF) (10 ng/mL) prolonged human neutrophil survival in culture by at least 36 hours. The addition of H-series compounds at concentrations that are considered to inhibit both protein kinase C (PKC) and cyclic adenylate monophosphate (cAMP)-dependent protein kinase (PKA) counteracted the effect of rhG-CSF. Concomitantly, the inhibition of nucleosomal DNA fragmentation by rhG-CSF was canceled. At lower concentrations, presumably capable of inhibiting only PKA, however, the compounds exhibited marginal effects on rhG-CSF-mediated increase of cell survival. These PKC inhibitors did not influence the priming effect of rhG-CSF significantly, as determined by O2- production stimulated by N-formyl-L-methionyl-L-leucyl phenylalanine (fMLP). Our results suggest that PKC plays an important role in the mechanism by which rhG-CSF promotes neutrophil survival, in striking contrast with the priming effect elicited by rhG-CSF.
Adachi
S
S
Department of Pediatrics, Kyoto University, Japan.
Kubota
M
M
Matsubara
K
K
Wakazono
Y
Y
Hirota
H
H
Kuwakado
K
K
Akiyama
Y
Y
Mikawa
H
H
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology; D004247:DNA / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000502:physiology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000097:blood*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology; D013481:Superoxides / Q000097:blood
D047428:Protein Kinase Inhibitors; D011994:Recombinant Proteins; D013481:Superoxides; D016179:Granulocyte Colony-Stimulating Factor; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004247:DNA; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C; D000469:Alkaline Phosphatase