Poly-unsaturated fatty acids alter the phenotype of human mast cells in vitro

Background: The increased n-6:n-3 poly-unsaturated fatty acid (PUFA) ratio in Western diets may contribute to the rapid increase in prevalence of allergic diseases. Key effector cells in allergy are mast cells (MC). Methods: The effect of different long chain (LC)- PUFA on MC activation was studied. Therefore separate n-6 (arachidonic acid, AA) and n-3 (eicosapentaenoic acid, EPA and docosahexaenoic acid, DHA) PUFA incorporation was investigated in human MC lines (LAD2, HMC-1). Effects of PUFA on IgE/anti-IgE mediated degranulation of LAD2 cells was studied. Furthermore PMA/ionomycin mediated mediator secretion (PGD2, TNF-alpha, IL-4 and IL-13), generation of reactive oxygen species (ROS) and phosphorylation of mitogen-activated protein kinases (MAPK) was examined using HMC-1 cells. ?Results: Incubation of MC with AA, EPA or DHA for 24 h increased the PUFA content of the cellular membrane. Incubation with PUFA did not reduce IgE-mediated degranulation by LAD2 cells. However, mediator release of ionomycin/PMA stimulated HMC-1 cells was differentially regulated. IL-13 (P <0.01 for all PUFA) and IL-4 (P <0.05 for EPA and DHA) secretion were inhibited, whereas AA enhanced TNF-alpha release (P <0.05). The effect of DHA on IL-13 release was most pronounced and associated with a reduction in ROS generation (P <0.01). AA incubation increased PGD2 secretion, whereas n-3 PUFA reduced PGD2. Cyclooxygenase (COX) inhibitors showed that the reduction in IL-13 secretion by PUFA was independent of COX. Preliminary results demonstrated that the ionomycin/PMA-induced phosphorylation of MAPK was inhibited by n-3 PUFA. Conclusion: Long-chain PUFA differentially alter mast cell activation which may affect the development of allergic diseases.