Formyl-methionyl-leucyl-phenylalanine and a calcium ionophore A23187 reverse the inhibition of phorbol myristate acetate-induced oxidative burst by linoleic and oleic acid anilides.
Linoleic and oleic acid anilides profoundly inhibited the production of reactive oxygen metabolites (ROM) in human polymorphonuclear leukocytes (PMNL) induced by a tumor promoter, phorbol myristate acetate (PMA). The addition of a Ca2+ ionophore, A23187, or a chemotactic peptide, formyl-methionyl-leucyl-phenylalanine (fMLP), readily reversed linoleic and oleic acid anilide-induced inhibiton of PMA-evoked respiratory burst in PMNL without affecting PMA-induced respiratory burst. fMLP or A23187 caused a marked increase in the production of ROM in PMNL that did not produce ROM after their co-exposure to PMA and cis-fatty acid anilides. This suggests a role for Ca2+ in this restoration of respiratory burst activity in PMNL. Oleic and linoleic acid anilides enhanced also respiratory burst in PMNL subsequent to their stimulation with fMLP. Interestingly, corresponding fatty acids, linoleic and oleic acid, also inhibited PMA-induced production of ROM in PMNL, but this inhibition was not reversed by A23187 or fMLP. These findings suggest that the aniline moiety of cis-fatty acids significantly modifies the effects of linoleic and oleic acids in the production of ROM in PMNL. Moreover, free intracellular Ca2+ may play a critical role in the activation of PMNL to produce ROM, and in the modulation of the effects of cis-fatty acid anilides.
Heiskanen
K M
KM
National Public Health Institute, Department of Toxicology, Kuopio, Finland.
Savolainen
K M
KM
D000813:Anilides / Q000633:toxicity*; D000001:Calcimycin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens / Q000037:antagonists & inhibitors / Q000633:toxicity; D004357:Drug Synergism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D008041:Linoleic Acids / Q000633:toxicity*; D008163:Luminescent Measurements; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology*; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009829:Oleic Acids / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000633:toxicity
D000813:Anilides; D002273:Carcinogens; D007476:Ionophores; D008041:Linoleic Acids; D009829:Oleic Acids; D017382:Reactive Oxygen Species; C039294:linoleylanilide; D000001:Calcimycin; C038731:oleoylanilide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium