Reactive oxygen production, arachidonate metabolism and cyclic AMP in macrophages

Chemiluminescence was used as an indicator of the production of reactive oxygen species by thioglycollate-elicited rat peritoneal macrophages stimulated by A23187. This action of the ionophore was inhibited by bromophenacyl bromide and nordihydroguaiaretic acid, inhibitors of the phospholipase A2 and lipoxygenase enzymes, respectively. The cyclo-oxygenase inhibitors, indomethacin and aspirin, did not diminish the light output. Preincubation of the cells with the 8-bromo- or dibutyryl analogues of cyclic AMP or with the cyclic AMP-phosphodiesterase inhibitors theophylline and RO-20-1724, or with PGE2, inhibited the A23187-evoked chemiluminescence. The results suggest that he lipoxygenase pathway of arachidonic acid metabolism may make a significant contribution to reactive oxygen production. This process may be modulated, and its duration limited, by cyclic AMP-mediated actions of prostaglandins, which are products of the cyclo-oxygenation of arachidonate.