Activation of human neutrophils by oleic acid involves the production of reactive oxygen species and a rise in cytosolic calcium concentration: a comparison with N-6 polyunsaturated fatty acids

Abstract

BACKGROUND: There is a growing body of evidence showing that dietary constituents and lipids in particular, influence the function of the human immune system. However, although the beneficial effects of oleic acid (OA) are clear, its mechanism of action at the molecular level is poorly understood. AIMS: To evaluate neutrophil activation under the influence of OA and compare this with several n-6 PUFAs. METHODS: Two key aspects of neutrophil activation were investigated: oxygen radical (ROS) production and intracellular Ca(2+) signaling. RESULTS: OA and the n-6 PUFA arachidonic acid (AA) both induced ROS production in a dose-dependent manner, although AA was the more potent stimulus. When looking for the mechanisms behind these effects, we found that both FA induce increases in cytosolic calcium concentration [Ca(2+)](i)), but whereas OA-induced ROS production is totally mediated through Ca2+ signaling, this is not the case for AA since ROS generation by AA is only partly inhibited in BAPTA-treated cells. We also found evidence for the involvement of protein kinase C (PKC) in the OA-induced ROS generation; by contrast, other enzymes apart from PKC seem to be implicated in n-6 PUFA-induced ROS production. In addition, our results argue against the involvement of a pertussis toxin-sensitive receptor activated by OA. CONCLUSIONS: OA differs from the n-6 PUFA AA in the activation of human neutrophils and these differences may be related to their distinct inmunomodulatory properties.