Effects of indomethacin, 5,8,11,14-eicosatetraynoic acid, and p-bromophenacyl bromide on lysosomal enzyme release and superoxide anion generation by human polymorphonuclear leukocytes

Preincubation of cytochalasin B-treated, human polymorphonuclear leukocytes (PMN) with indomethacin (a cyclo-oxygenase inhibitor), 5,8,11,14-eicosatetraynoic acid (ETYA) (a lipoxygenase/cyclo-oxygenase inhibitor), or p-bromophenacyi bromide (BPB) (a phospholipase A₂ inhibitor) resulted in dose-dependent inhibition of lysosomal enzyme release elicited by the chemotactic peptide N-formylmethionylleucylphenylalanine (FMLP); 50 per cent inhibition was seen at approximately 50, 12, 8 μM respectively. BPB also inhibited Superoxide anion generation. The effects of indomethacin and ETYA were dependent upon the type of stimulus presented to the cells. Lysosomal enzyme release stimulated by zymosan-treated serum and serum-treated zymosan was relatively unaffected by these two inhibitors. Indomethacin and ETYA did not appear to exert their effects by specific inhibition of prostaglandin and thromboxane synthesis; the inhibition offered by both agents was reversible, and aspirin had no similar inhibitory capacity. Our results indicate not only that indomethacin may exert effects independent of its inhibition of the cyclo-oxygenase pathway but also that products formed via phospholipase and lipoxygenase may be mediators of lysosomal enzyme release and superoxide anion generation.