Related Experiment Videos
In vivo formation of leukotriene E5 by murine peritoneal cells
J Whelan1, K S Broughton, B Lokesh
1Lipids Research Laboratory, Institute of Food Science, Cornell University, Ithaca, NY 14853.
Abstract:
Resident mouse peritoneal cells, stimulated in vivo with opsonized zymosan, produced leukotriene C4 and E4, with LTE4 being the major (80-90%) product. When mice were placed on diets containing increasing amounts of fish oil, four additional sulfidopeptide leukotrienes (SP-LT), LTC5, LTE5, 11-trans LTC5 and 11-trans LTE5, were identified. The identity of LTE5 was confirmed by spectrophotometric, chromatographic and enzymatic methods. When equivalent amounts of n-6 and n-3 polyunsaturated fatty acids (PUFA) were included in the diet, the stimulated peritoneal cells (in vivo) produced higher quantities of LTE5 (30.2 +/- 5.4 ng/10(6) cells) than LTE4 (22.8 +/- 7.3 ng/10(6) cells). In addition, in vitro studies demonstrated a 60% reduction in LTC4 (42.0 +/- 10.8 ng/10(6) cells to 16.7 +/- 6.2 ng/10(6) cells) and the appearance of LTC5 (2.1 +/- 0.9 ng/10(6) cells) in resident macrophages (stimulated with A23187) from mice maintained on a fish oil diet compared to mice fed the control diet. This study demonstrated that formation of the pentaenyl SP-LT in vivo, in particular LTE5, by peritoneal cells can significantly contribute to the endogenous SP-LT pool in response to an inflammatory stimulus following a dietary regimen containing fish oil.
Insights
Dietary fish oil supplementation in mice alters leukotriene production. Mice on fish oil diets produced novel pentaenyl sulfidopeptide leukotrienes (SP-LT), like leukotriene E5 (LTE5), impacting inflammatory responses.
Area of Science:
- Immunology
- Biochemistry
- Nutrition Science
Background:
- Resident mouse peritoneal cells produce leukotriene C4 (LTC4) and E4 (LTE4) upon stimulation.
- LTE4 is the predominant sulfidopeptide leukotriene (SP-LT) produced under normal dietary conditions.
Purpose of the Study:
- To investigate the impact of dietary fish oil, rich in n-3 polyunsaturated fatty acids (PUFA), on SP-LT production in mice.
- To identify and characterize novel SP-LTs generated in response to fish oil-enriched diets.
Main Methods:
- Mice were fed diets with varying amounts of fish oil.
- Peritoneal cells were stimulated in vivo with opsonized zymosan and in vitro with A23187.
- Leukotriene production was analyzed using spectrophotometric, chromatographic, and enzymatic methods.
Main Results:
- Fish oil diets led to the identification of four new SP-LTs, including leukotriene E5 (LTE5).
- LTE5 became a major SP-LT, with quantities exceeding LTE4 in stimulated peritoneal cells from mice on n-3 PUFA-rich diets.
- In vitro studies showed reduced LTC4 and increased LTC5 production in macrophages from fish oil-fed mice.
Conclusions:
- Dietary fish oil significantly alters the profile of SP-LTs produced by peritoneal cells.
- The formation of pentaenyl SP-LTs, particularly LTE5, contributes to the endogenous SP-LT pool during inflammatory stimuli in mice fed fish oil.
- This highlights a mechanism by which dietary n-3 PUFA can modulate inflammatory pathways.