A synthetic peptide containing a predominant protein kinase C site within p47phox inhibits the NADPH oxidase in intact neutrophils

In vivo loading of a synthetic peptide (peptide 4) corresponding to residues 314–331 (RSRKRLSQDAYRRNSVRF) consistently diminished the oxidative burst in response to either phorbol 12‐myristate 13‐acetate (PMA) or formylmethionyl‐leucyl‐phenylalanine and cytochalasin B (fMLP/CB) compared to other synthetic peptides derived from the p47phox 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 p47phox. The PMA‐induced translocation of p47phox to the plasma membrane was diminished in neutrophils loaded with peptide 4. These data represent the first report of a synthetic peptide derived from p47phox that inhibits the NADPH oxidase in intact neutrophils and inhibits the protein kinase C–mediated phosphorylation of endogenous p47phox.