FORMYL-METHIONYL-LEUCYL-PHENYLALAMINE AND A CALCIUM IONOPHORE A23187 REVERSE THE INHIBITION OF PHORBOL-MYRISTATE ACETATE-INDUCED OXIDATIVE BURST BY LINOLEIC AND OLEIC-ACID ANILIDES
Km. Heiskanen et Km. Savolainen, FORMYL-METHIONYL-LEUCYL-PHENYLALAMINE AND A CALCIUM IONOPHORE A23187 REVERSE THE INHIBITION OF PHORBOL-MYRISTATE ACETATE-INDUCED OXIDATIVE BURST BY LINOLEIC AND OLEIC-ACID ANILIDES, Toxicology, 110(1-3), 1996, pp. 39-45
Linoleic and oleic acid anilides profoundly inhibited the production o
f reactive oxygen metabolites (ROM) in human polymorphonuclear leukocy
tes (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 linole
ic and oleic acid anilide-induced inhibition of PMA-evoked respiratory
burst in PMNL without affecting PMA-induced respiratory burst. fMLP o
r A23187 caused a marked increase in the production of ROM in PMNL tha
t did not produce ROM after their co-exposure to PMA and cis-fatty aci
d anilides. This suggests a role for Ca2+ in this restoration of respi
ratory burst activity in PMNL. Oleic and linoleic acid anilides enhanc
ed also respiratory burst in PMNL subsequent to their stimulation with
fMLP. Interestingly, corresponding fatty acids, linoleic and oleic ac
id, also inhibited PMA-induced production of ROM in PMNL, but this inh
ibition was not reversed by A23187 or fMLP. These findings suggest tha
t the aniline moiety of cis-fatty acids significantly modifies the eff
ects of linoleic and oleic acids in the production of ROM in PMNL. Mor
eover, free intracellular Ca2+ may play a critical role in the activat
ion of PMNL to produce ROM, and in the modulation of the effects of ci
s-fatty acid anilides.