Indication of a Protein Kinase C-Independent Pathway for NADPH Oxidase Activation in Human Neutrophils

A potent tyrosine phosphatase inhibitor, pervanadate, induced (i) translocation of the cytosolic NADPH oxidase factors, p47-phoxand p67-phox,to the plasma membrane; and (ii) O−2production in human neutrophils. However, the translocation of p47-phoxand p67-phoxwas inhibited by H-7, a protein kinase C (PKC) inhibitor without markedly affecting O−2production in whole neutrophils. Results from the plasma membrane fraction showed that NADPH oxidase activity in neutrophils treated with pervanadate did not vary in the presence or absence of H-7, despite a lower content of p47-phoxand p67-phoxin H-7-treated neutrophils. These findings suggest that in addition to the well-known PKC-dependent pathway, there may exist another PKC-independent pathway to activate NADPH oxidase in human neutrophils. This pathway involves protein tyrosine phosphorylation but does not seem to necessitate translocation of p47-phoxand p67-phoxto the plasma membrane.