Bimodal action of fatty acids on PMA-stimulated O2.- production in human adherent monocytes

Abstract

Not only unsaturated linear fatty acids, but also saturated monomethyl-branched fatty acids (MMBFAs), are provided by food. They are capable of penetrating into the membrane lipids and promoting lipid disorder. Both NADPH oxidase and protein kinase C (PKC) are bound to cell cytoplasmic membranes and are responsive to unesterified fatty acids (UEFAs). We found that the O2.- NADPH oxidase-mediated production of human adherent monocytes was modified by unsaturated linear and saturated branched UEFAs only in the presence of phorbol myristate acetate. This result together with our inhibition data indicated an action strictly linked to PKC activity. The type and intensity of action depended on the UEFA concentrations and chain structure. Nanomolar concentrations showed potentiating effects whereas micromolar (< CMC) concentrations displayed depressant influences MMBFAs were generally more active than the other FAs. With respect to the micromolar depressant effect, oleate and linoleate were as active and docosahexaenoate nearly as active as MMBFAs. As assessed by iso-15:0 or arachidonate action, such bimodal alteration did not occur in non-adherent monocytes and neutrophils. Certain UEFAs could be considered as 'cellular' anti-oxidants on the sites of adherent-monocyte recruitment.