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 Ca²⁺ 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 [Ca²⁺]_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.

Fatty acids as modulators of neutrophil recruitment, function and survival

“…These observations were obtained in rat isolated-neutrophils and confirmed in human neutrophils (Hatanaka et al, 2006). Carrillo et al (2011) described that oleic acid-induced reactive oxygen species production is mediated by protein kinase C and Ca 2+ signalling. So, the oxidative burst induced by oleic acid appears to be a consequence of protein kinase C activation induced by elevation in intracellular Ca 2+ concentrations (Carrillo et al, 2011).…”

“…Carrillo et al (2011) described that oleic acid-induced reactive oxygen species production is mediated by protein kinase C and Ca 2+ signalling. So, the oxidative burst induced by oleic acid appears to be a consequence of protein kinase C activation induced by elevation in intracellular Ca 2+ concentrations (Carrillo et al, 2011). These results were partially confirmed by Hidalgo et al (2011).…”

Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin

“…Nevertheless, Kudo et al [67] provide evidence that chronic exposure to oleic acid led to the continuous excitation of β-cells, depletion of insulin storage, and impairment of glucose-stimulated insulin secretion (GSIS). This discrepancy can be justified by the fact that oleic acid increased the expression of GLUT2, which may partially contribute to the increased basal insulin secretion [68] but enhanced the levels of intracellular free Ca 2+ , which most likely accounts for the decrease of GSIS [69]. …”

P2X1 expressed on polymorphonuclear neutrophils and platelets is required for thrombosis in mice

“…21,22 To determine whether PMNs accumulating at the site of injury are activated, exogenously Fluo-4-AM-labeled PMNs from WT mice were infused into a WT recipient mouse. Calcium mobilization (depicted in green in Figure 1A) in exogenous PMNs accumulating in the developing thrombus was detected following an excitation at 488 nm.…”