Superoxide production in human neutrophils: evidence for signal redundancy and the involvement of more than one PKC isoenzyme class.
Selective protein kinase C (PKC) activators and inhibitors and a physiological agonist, fMLP, were used to study superoxide production and PKC isoenzyme activation in human neutrophils. The data show that the classical PKC isoenzymes, alpha and beta, were activated by TPA and at a time prior to NADPH oxidase complex assembly. fMLP induced activation of PKC-beta over a similar time course. Inhibition of c-PKCs reduced, but did not block, TPA-induced superoxide production completely, suggesting additional PKC isoenzymes were involved beyond NADPH oxidase assembly. PKC inhibitors were unable to inhibit fMLP-induced superoxide generation, indicative of signal redundancy in the induction of superoxide generation in human neutrophils.
Pongracz
J
J
Department of Immunology, University of Birmingham, United Kingdom.
Lord
J M
JM
D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate