THE FATTY-ACID BIMODAL ACTION ON SUPEROXIDE ANION PRODUCTION BY HUMAN ADHERENT MONOCYTES UNDER PHORBOL 12-MYRISTATE 13-ACETATE OR DIACYLGLYCEROL ACTIVATION CAN BE EXPLAINED BY THE MODULATION OF PROTEIN-KINASE-C AND P47(PHOX) TRANSLOCATION

We studied the translocation of protein kinase C (PKC), the endogenous phosphorylation and presence in the membrane fraction of p47(phox) (the 47-kDa cytosolic component of the phagocyte NADPH oxidase), and the O-2-radical-anion production in human adherent monocytes (HAMs). This was performed under phorbol myristate acetate (PMA) or diacylglycerol stimulation after cell preincubation in the presence of either 13-methyltetradecanoate or arachidonate. At 3 nM and 30 mu M, both fatty acids had enhancing and depressing effects, respectively, on PKC translocation and O-2-radical-anion production strictly depending on the PMA- or diacylglycerol-stimulated state of the cell. Endogenous phosphorylation and membrane presence of p47(phox) were markedly reinforced in PMA-stimulated HAMs in the presence as compared to the absence of 13-methyltetradecanoate. These results emphasize the fact that in intact cells the capacity of both FAs to potentiate or depress the HAM O-2-radical-anion production is mediated by a direct action on the PKC membrane translocation leading to a simultaneous endogenous phosphorylation and membrane translocation of p47(phox). They confirm the recent findings (Kadri-Hassani, N., Leger, C. L., and Descomps, B. (1995) J. Lipid Med. Cell Signal. 11, 159-173) on the PKC-mediated, adherent monocyte-specific capacity of these fatty acids and others (with the exception of linear saturated fatty acids) to enhance the PMA-stimulated O-2-radical-anion production at nanomolar concentrations and to depress it at micromolar concentrations.