Distinct involvement of p38-, ERK1/2 and PKC signaling pathways in C5a-mediated priming of oxidative burst in phagocytic cells.
C5a exerts various known harmful functions during experimental sepsis and blocking strategies demonstrated survival benefits in experimental sepsis. We investigated its potential for priming of oxidative burst in blood neutrophils and monocytes and the involvement of various signaling pathways. We here report that C5a induced priming of neutrophils and monocytes for Escherichia coli- and PMA-induced oxidative burst. This effect was strongly dependent on intact ERK1/2 signaling. P38 inhibition resulted in abrogation of C5a-induced priming only for E. coli-induced oxidative burst and PKC blockade had this effect only for PMA-induced burst. JNK inhibition had no impact. Our results demonstrate for the first time distinct involvement of ERK1/2, p38 and PKC pathways for C5a-induced priming of oxidative burst in phagocytes.
Wrann
Christiane D
CD
Department of Trauma Surgery, Hannover Medical School, Carl Neuberg Str. 1, 30625 Hannover, Germany.
Winter
Sebastian W
SW
Barkhausen
Tanja
T
Hildebrand
Frank
F
Krettek
Christian
C
Riedemann
Niels C
NC
D015936:Complement C5a / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000276:immunology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000276:immunology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D016897:Respiratory Burst / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate