title: n-3 Polyunsaturated fatty acids inhibit Fc ε receptor I-mediated mast cell activation.
abstract: In vivo models show that n-3 polyunsaturated fatty acids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc ε receptor I (FcεRI)-mediated signal transduction and mast cell activation. Bone marrow-derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fatty acid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n-3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less β-hexosaminidase (β-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (β-hex release) following FcεRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and FcεRI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell FcεRI was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced FcεRI localization to lipid rafts, and stimulation with antigen resulted in aberrant FcεRI shuttling to the rafts. Our results show that n-3 PUFA suppress FcεRI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FcεRI to lipid rafts.
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Human Health and Nutritional Sciences, College of Biological Sciences, University of Guelph, Guelph, ON, Canada.
authors.forename: David W L
authors.initials: DW
authors.lastname: Ma
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors.forename: Jing X
authors.initials: JX
authors.lastname: Kang
authors.affiliation: National Institute for Nanotechnology, Edmonton, AB, Canada. Electronic address: marianna.kulka@nrc-cnrc.gc.ca.
authors.forename: Marianna
authors.initials: M
authors.lastname: Kulka
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000941:Antigens / Q000737:chemistry; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival; D019587:Dietary Supplements; D015525:Fatty Acids, Omega-3 / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008407:Mast Cells / Q000166:cytology*; D021962:Membrane Microdomains / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D017455:Receptors, IgE / Q000378:metabolism*; D015398:Signal Transduction; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: D000941:Antigens; D015525:Fatty Acids, Omega-3; D017455:Receptors, IgE; D001619:beta-N-Acetylhexosaminidases
keywords: FcεRI; Lipid rafts; Mast cell; Signal transduction; n-3 Polyunsaturated fatty acids