Fish oil increases raft size and membrane order of B cells accompanied by differential effects on function.
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. 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.
Department of Biochemistry and Molecular Biology, Brody School of Medicine, East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC 27834, USA.
Benjamin Drew
BD
Rockett
Heather
H
Teague
Mitchel
M
Harris
Mark
M
Melton
Justin
J
Williams
Stephen R
SR
Wassall
Saame Raza
SR
Shaikh
D000818:Animals; D001402:B-Lymphocytes / Q000737:chemistry / Q000187:drug effects*; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000187:drug effects; D002478:Cells, Cultured; D003432:Cross-Linking Reagents / Q000737:chemistry; D003902:Detergents / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005395:Fish Oils / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010714:Phosphatidylethanolamines / Q000737:chemistry
D003432:Cross-Linking Reagents; D003902:Detergents; D005395:Fish Oils; D008070:Lipopolysaccharides; D010714:Phosphatidylethanolamines; D004281:Docosahexaenoic Acids; D005677:G(M1) Ganglioside; D015118:Eicosapentaenoic Acid