Effects of purified dietary n-3 ethyl esters on murine T lymphocyte function.
To precisely determine the biologic role of fish oil-derived constituents (n-3 polyunsaturated fatty acids), it is imperative that information on highly purified n-3 polyunsaturated fatty acids be evolved. Therefore, we studied the effects of a low dose, short term dietary supplementation with highly purified (n-3) ethyl esters with regard to murine T lymphocyte function. A 10-day dietary supplementation with low dose, highly purified (n-3) fatty acid ethyl esters was examined for effects on murine splenic lymphocyte function and membrane composition. Mice were fed diets containing either 3% safflower oil (SAF) ethyl esters, 2% SAF plus 1% eicosapentaenoic acid ethyl esters (EPA) (99% pure), or 2% SAF plus 1% docosahexaenoic acid ethyl esters (DHA) (97% pure). Fatty acid analysis of the lymphocyte membranes showed that membrane compositions of the EPA- and DHA-fed mice were subsequently enriched with these (n-3) fatty acids. Con A-induced lymphoproliferative assays (Con A, 5 and 10 micrograms/ml) revealed that splenic lymphocytes from the EPA group had significantly higher mitogenic responses relative to lymphocytes from the DHA or SAF groups (p < 0.05). In contrast, DHA splenocytes had the highest level of 3H-labeled diradylglycerol as a percentage of total lipid. Macrophage-lymphocyte co-cultures demonstrated that the dietary effect on proliferation in response to Con A was influenced by lymphocyte source, but apparently not by macrophage source. In addition, cells from Mycobacterium bovis vaccine-vaccinated mice were placed in culture with purified protein derivative (PPD) (10, 20, and 40 micrograms/ml), as well as Con A (5 and 10 micrograms/ml) to allow comparison between mitogenic and antigenic stimulation. No statistically significant differences (p > 0.05) existed between the diet groups upon PPD stimulation. However, lymphocytes from the DHA group exhibited significantly higher proliferative responses to Con A than cells from the EPA and SAF groups (p < 0.05). M. bovis vaccine-immunized EPA and DHA fed mice also exhibited significantly reduced delayed-type hypersensitive reactivity to footpad testing with PPD in comparison to that demonstrated by SAF-fed mice (p < 0.05). EPA-fed mice demonstrated the most decreased response. Overall, this study demonstrates for the first time that: 1) low dose, short term dietary supplementation with highly purified EPA or DHA can modulate select functional and transmembrane signaling responses of murine splenic lymphocytes; and 2) that these dietary agents have differing effects on mitogen vs Ag receptors.
Fowler
K H
KH
Department of Animal Science, Texas A&M University, College Station 77843-2471.
Chapkin
R S
RS
McMurray
D N
DN
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004032:Diet; D004075:Diglycerides / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D007375:Interleukin-1 / Q000096:biosynthesis; D050356:Lipid Metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D000893:Anti-Inflammatory Agents; D004075:Diglycerides; D007375:Interleukin-1; D004281:Docosahexaenoic Acids; C035276:eicosapentaenoic acid ethyl ester; C067518:4,7,10,13,16,19-docosahexaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid