n-3 polyunsaturated fatty acids inhibit Fc ε receptor I-mediated mast cell activation

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DOIResolve DOI: http://doi.org/10.1016/j.jnutbio.2015.07.027
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TypeArticle
Journal titleThe Journal of Nutritional Biochemistry
ISSN0955-2863
Volume26
Issue12
Pages15801588
Subjectn-3 polyunsaturated fatty acids; mast cell; FcεRI; signal transduction; lipid rafts
AbstractIn 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.
Publication date
PublisherElsevier
LanguageEnglish
AffiliationNRC Institute for Research in Construction; National Institute for Nanotechnology; National Research Council Canada
Peer reviewedYes
NPARC number23001564
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Record identifier073af9b5-7485-4c17-b48a-934027f83984
Record created2017-03-07
Record modified2017-05-15
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