PHOSPHATIDIC-ACID INDUCES THE RESPIRATORY BURST OF ELECTROPERMEABILIZED HUMAN NEUTROPHILS BY ACTING ON A DOWNSTREAM STEP OF PROTEIN-KINASE-C

Phosphatidic acid (PA) dose-dependently induced superoxide (O2-) produ ction of electropermeabilized human neutrophils but not of intact neut rophils, indicating that PA induces the activation of NADPH oxidase by acting on an intracellular target. The O2- production by PA was not i nhibited by protein kinase C (PKC) inhibitors, such as staurosporine a nd calphostin C, and an inhibitor of PA phosphohydrolase, propranolol. These observations suggest that the activation of the oxidase by PA i s independent of the activity of PKC and may dominate the activation b y diacylglycerol which is formed from PA via the action of PA phosphoh ydrolase. Furthermore, the production by PA, as well as that by phorbo l myristate acetate, was inhibited by cyclic AMP and GDPbetaS. Therefo re, PA seems to act at a site downstream of PKC.