Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function

被引:87
作者
Rockett, Benjamin Drew [1 ]
Teague, Heather [1 ]
Harris, Mitchel [1 ]
Melton, Mark [1 ]
Williams, Justin [2 ]
Wassall, Stephen R. [2 ]
Shaikh, Saame Raza [1 ]
机构
[1] E Carolina Univ, E Carolina Diabet & Obes Inst, Brody Sch Med, Dept Biochem & Mol Biol, Greenville, NC 27834 USA
[2] Indiana Univ Purdue Univ, Dept Phys, Indianapolis, IN 46202 USA
基金
美国国家卫生研究院;
关键词
antigen-presenting cell; cytokines; detergent resistant membrane; docosahexaenoic acid; lymphocytes; POLYUNSATURATED FATTY-ACIDS; DOCOSAHEXAENOIC ACID; T-CELLS; LIPID RAFTS; N-3; PUFA; ANTIGEN PRESENTATION; CLASS-I; ACTIVATION; ORGANIZATION; MACROPHAGES;
D O I
10.1194/jlr.M021782
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Fish oil (FO) targets lipid microdomain organization to suppress T-cell and macrophage function; however, little is known about this relationship with B cells, especially at the animal level. We previously established that a high FO dose diminished mouse B-cell lipid raft microdomain clustering induced by cross-linking GM1. To establish relevance, here we tested a FO dose modeling human intake on B-cell raft organization relative to a control. Biochemical analysis revealed more docosahexaenoic acid (DHA) incorporated into phosphatidylcholines than phosphatidylethanolamines of detergent-resistant membranes, consistent with supporting studies with model membranes. Subsequent imaging experiments demonstrated that FO increased raft size, GM1 expression, and membrane order upon cross-linking GM1 relative to no cross-linking. Comparative in vitro studies showed some biochemical differences from in vivo measurements but overall revealed that DHA, but not eicosapentaenoic acid (EPA), increased membrane order. Finally, we tested the hypothesis that disrupting rafts with FO would suppress B-cell responses ex vivo. FO enhanced LPS-induced B-cell activation but suppressed B-cell stimulation of transgenic naive CD4(+) T cells.(jlr) Altogether, our studies with B cells support an emerging model that FO increases raft size and membrane order accompanied by functional changes; furthermore, the results highlight differences in EPA and DHA bioactivity.-Rockett, B. D., H. Teague, M. Harris, M. Melton, J. Williams, S. R. Wassall, and S. R. Shaikh. Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function. J. Lipid Res. 2012. 53: 674-685.
引用
收藏
页码:674 / 685
页数:12
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