Effect of the 5-lipoxygenase inhibitor piriprost on superoxide production by human neutrophils

The effect of 6,9-deepoxy-6,9-(phenylimino)-delta 6,8-prostaglandin I1 (Piriprost) on the oxidative response was studied in human neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), phorbol 12-myristate, 13-acetate (PMA) or opsonized zymosan. Piriprost inhibited the stimulatory effect of fMLP on superoxide anion (O2-) generation, at concentrations higher than those which depress leukotriene B4 (LTB4) formation. This inhibition was overcome by increasing the concentration of fMLP. Neither exogenous LTB4 nor indomethacin were able to reverse the inhibitory effect of piriprost on fMLP action. In contrast, piriprost did not inhibit the stimulation of O2- production induced by PMA or zymosan. Piriprost behaves thus as a specific and apparently competitive antagonist of fMLP: this action does not seem to involve lipoxygenase inhibition and might be exerted at the level of the fMLP receptor or its associated mechanisms of transduction.