The respiratory burst of human neutrophils treated with various stimulators in vitro is dampened by exogenous unsaturated fatty acids.
Cis-unsaturated free fatty acids (FFA) at concentrations between 10 and 30 microM suppressed the superoxide respiratory burst induced in human neutrophils by the chemotactic peptide, N-formylmethionyl-leucyl-phenylalanine (FMLP). Corresponding trans-isomers had a reduced efficacy while saturated FFA were inert. The effects of unsaturated FFA were maximally achieved after several min of preincubation with cells and reversed upon washing. Increased concentrations of Ca2+ in the medium also relieved the inhibition. Unsaturated FFA were equally effective in dampening the respiratory burst induced by fluoride ions but less so with bursts elicited by 9 nM phorbol myristate acetate (PMA). Moreover reactions triggered by higher concentrations (e.g., 100 nM) of PMA were resistant to the effects of FFA. Radioimmunoassays showed that unsaturated FFA directly elevated intracellular cyclic adenosine monophosphate (cAMP) by severalfold above basal levels. It is suggested that inhibition is brought about by unsaturated FFA perturbation of the neutrophil membrane structure, perhaps with an independent contribution from a cAMP-dependent mechanism.
D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005459:Fluorides / Q000494:pharmacology; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D005231:Fatty Acids, Unsaturated; D015117:5,8,11,14-Eicosatetraynoic Acid; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides; D002118:Calcium