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 p47phox translocation.

We studied the translocation of protein kinase C (PKC), the endogenous phosphorylation and presence in the membrane fraction of p47phox (the 47-kDa cytosolic component of the phagocyte NADPH oxidase), and the O-.2 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 microM, both fatty acids had enhancing and depressing effects, respectively, on PKC translocation and O-.2 production strictly depending on the PMA- or diacylglycerol-stimulated state of the cell. Endogenous phosphorylation and membrane presence of p47phox 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 production is mediated by a direct action on the PKC membrane translocation leading to a simultaneous endogenous phosphorylation and membrane translocation of p47phox. They confirm the recent findings (Kadri-Hassani, N., Léger, 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 production at nanomolar concentrations and to depress it at micromolar concentrations.