A synthetic peptide containing a predominant protein kinase C site within p47(phox) inhibits the NADPH oxidase in intact neutrophils

In vivo loading of a synthetic peptide (peptide 4) corresponding to residues 314-331 (RSRKRLSQDAYRNSVRF) consistently diminished the oxidative burst in response to either phorbol 12-myristate 13-aeetate (PMA) or formylmethionyl-leucyl-phenylalamine and cytochalasin B (fMLP/CB) compared to other synthetic peptides derived from the P47(phox) sequence. The effects of peptide 4 were concentration dependent with respect to both PMA and fMLP/CB. In contrast, peptide 4 enhanced the oxidative burst in response to fMLP alone, Peptide 4 inhibited the PMA and fMLP-mediated phosphorylation of endogenous neutrophil cytosolic proteins including P47(phox). The PMA-induced translocation of P47(phox) to the plasma membrane was diminished in neutrophils loaded with peptide 4. These data represent the first report of a synthetic: peptide derived from p47(phox) that inhibits the NADPH oxidase in intact neutrophils and inhibits the protein kinase C-mediated phosphorylation of endogenous P47(phox).