n-3 Polyunsaturated fatty acids inhibit Fc epsilon receptor I-mediated mast cell activation

卷:26

Wang, Xiaofeng ; Ma, David W. L. ; Kang, Jing X. ; Kulka, Marianna

Natl Res Council Canada

关键词: n-3 Polyunsaturated fatty acids;    Mast cell;    Fc epsilon RI;    Signal transduction;    Lipid rafts;   

DOI  :  10.1016/j.jnutbio.2015.07.027

学科分类：食品科学和技术

【 摘 要 】

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 a receptor I (Fc epsilon RI)-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 beta-hexosaminidase (beta-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 (beta-hex release) following FceRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and Fc epsilon RI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell REM was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced Fc epsilon RI localization to lipid rafts, and stimulation with antigen resulted in aberrant REM shuttling to the rafts. Our results show that n-3 PUFA suppress Fc epsilon RI-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 FceRI to lipid rafts. Crown Copyright (C) 2015 Published by Elsevier Inc. All rights reserved.