Neutrophil generation of inflammatory precursors is not modulated by docosahexaenoic acid
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Objective and design
It is believed that correction of membrane fatty acid deficiency in cystic fibrosis (CF) downregulates the synthesis of proinflammatory mediators. We tested the hypothesis that an increase of the proportion of docosahexaenoic acid (DHA) in the membrane in vitro changes the neutrophil response to Pseudomonas aeruginosa lipopolysaccharide (LPS).
Treatment with DHA increased the secretion of interleukin(IL)-1|*alpha*| by CF neutrophils, but the secretion of other cytokines, CD11b expression, and arachidonic acid (AA) release were not affected either in CF or control (CT) neutrophils. Both with and without DHA, only one out of eight CF neutrophils responded to LPS with an increase of released AA, while five out of seven CT cells released more AA (CF vs. CT P < 0.05 by Fisher test).
These results indicate that in neutrophils the beneficial effects of DHA on immune response are not directly related to the generation of proinflammatory precursors, and suggest that in CF the lower neutrophil AA generation in response to activation could cause insufficient production of lipid mediators involved in the resolution of lung inflammation.
KeywordsDocosahexaenoic acid Arachidonic acid Neutrophil function Lipid mediator precursor Cystic fibrosis
Cytosolic phospholipase A2
Fetal bovine serum
Polyunsaturated fatty acids
Pseudomonas aeruginosa lipopolysaccharide
Our gratitude to La Lega Italiana per la lotta alla Fibrosi Cistica which has supported this work. We are thankful for Dr. Mauro Biffoni’s excellent collaboration. We would like to thank Dr. Emanuele Bernardi for his technical help and Dr. E. Fanales Belasio for his scientific advice. We are grateful to Prof. K.M. Botham who has contributed to the improvement of the manuscript with scientific advice and revision of the English language.
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