INDICATION OF A PROTEIN-KINASE C-INDEPENDENT PATHWAY FOR NADPH OXIDASE ACTIVATION IN HUMAN NEUTROPHILS

A potent tyrosine phosphatase inhibitor, pervanadate, induced (i) tran slocation of the cytosolic NADPH oxidase factors, p47-phox and p67-pho x, to the plasma membrane; and (ii) Oy production in human neutrophils . However, the translocation of p47-phox and p67-phox was inhibited by H-7, a protein kinase C (PKC) inhibitor without markedly affecting O- 2(-) production in whole neutrophils. Results from the plasma membrane fraction showed that NADPH oxidase activity in neutrophils treated wi th pervanadate did not vary in the presence or absence of H-7, despite a lower content of p47-phox: and p67-phox: in H-7-treated neutrophils . These findings suggest that in addition to the well-known PKC-depend ent pathway, there may exist another PKC-independent pathway to activa te NADPH oxidase in human neutrophils. This pathway involves protein t yrosine phosphorylation but does not seem to necessitate translocation of p47-phox and p67-phox to the plasma membrane. (C) 1998 Academic Pr ess.