The Influence of Polyunsaturated Fatty Acids on the Phospholipase D Isoforms Trafficking and Activity in Mast Cells

Abstract

The impact of polyunsaturated fatty acid (PUFA) supplementation on phospholipase D (PLD) trafficking and activity in mast cells was investigated. The enrichment of mast cells with different PUFA including α-linolenic acid (LNA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), linoleic acid (LA) or arachidonic acid (AA) revealed a PUFA-mediated modulation of the mastoparan-stimulated PLD trafficking and activity. All PUFA examined, except AA, prevented the migration of the PLD1 to the plasma membrane. For PLD2 no PUFA effects on trafficking could be observed. Moreover, PUFA supplementation resulted in an increase of mastoparan-stimulated total PLD activity, which correlated with the number of double bonds of the supplemented fatty acids. To investigate, which PLD isoform was affected by PUFA, stimulated mast cells were supplemented with DHA or AA in the presence of specific PLD-isoform inhibitors. It was found that both DHA and AA diminished the inhibition of PLD activity in the presence of a PLD1 inhibitor. By contrast, only AA diminished the inhibition of PLD activity in the presence of a PLD2 inhibitor. Thus, PUFA modulate the trafficking and activity of PLD isoforms in mast cells differently. This may, in part, account for the immunomodulatory effect of unsaturated fatty acids and contributes to our understanding of the modulation of mast cell activity by PUFA.

Treating canine atopic dermatitis with unsaturated fatty acids: the role of mast cells and potential mechanisms of action

“…Furthermore, PUFA increase the stimulation‐induced total PLD activity as shown for blood mononuclear cells (Bechoua et al., ), the fibroblast‐like monkey cell line COS‐1 (Gemeinhardt et al., ) as well as for the canine mast cell line C2 (Basiouni et al., ). All the PUFA tested including LNA, EPA, DHA, LA and AA emerged to promote the total enzymatic activity of mast cell PLD (Basiouni et al., ). Inhibition studies using isoform‐specific inhibitors of either PLD1 or PLD2 provided further evidence that AA has an enhancing effect on both PLD isoforms (Basiouni et al., ).…”

“…Even though PUFA supplementation is widely used in atopic patients, their mode of action remains unclear. Some interesting insights into the impact of PUFA on mast cell exocytosis were provided by in vitro studies using the canine mast cell line C2 (Gueck et al., , ,b; Seidel et al., ; Schmutzler et al., ; Basiouni et al., , ). Due to the impaired function of the IgE receptor expressed by C2 cells (Hunter et al., ), the wasp venom peptide mastoparan, which triggers a G protein receptor, was used for stimulation.…”

“…A PUFA‐mediated modulation of the PLD also applies to mast cells. PUFA have been shown to affect the intracellular localization of PLD1 and to influence the enzymatic activity of total PLD (Gemeinhardt et al., ; Basiouni et al., ).…”

“…Mast cell activation is associated with a translocation of PLD1 from intracellular vesicular structures to the plasma membrane (Brown et al., ; Choi et al., ). The stimulation‐induced movement of PLD1 is inhibited by the enrichment of mast cells with LA, LNA, EPA or DHA, but not with AA (Basiouni et al., ). As the translocation is considered to be essential for PLD1‐mediated exocytosis, this observation provides an explanation for the decreased mediator release of mast cells supplemented with LA, LNA, EPA or DHA (Gueck et al., , ,b).…”

Linoleic acid supplementation of cell culture media influences the phospholipid and lipid profiles of human reconstructed adipose tissue

“…One of the principal molecules found in AT are lipids, which actively regulate metabolic processes both inside adipocytes (triglycerides, energy storage) and in cell membranes (glycerophospholipids, signaling) [1]. Indeed, polyunsaturated fatty acids (PUFAs) influence vital aspects of the cellular physiology, including membrane fluidity [2], metabolism [3–5], protein folding and functionality [6], lipid rafts [7, 8], signaling [9, 10], trafficking processes [11, 12] and inflammation [13]. While saturated fatty acids (FAs) can be produced by mammalian cells from sugar (lipogenesis), PUFAs need to be provided from the diet.…”