HYDROGEN PEROXIDE PRODUCTION STIMULATED BY N-FORMYL-METHIONYL-LEUCYL-PHENYLALANINE IN GUINEA PIG MACROPHAGES AND EFFECTS OF ANTI-INFLAMMATORY DRUGS AND LOCAL ANESTHETICS

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N-formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated hydrogen peroxide (H_2O_2) production in peritoneal macrophages and the effects of antiinflammatory drugs and local anesthetics on it were electron cytochemically demonstrated using the cerium method. Resident peritoneal macrophages were harvested from adult male guinea pigs and treated with 5 μg/ml cytochalasin B for 15 min followed by an FMLP (1 μM) treatment for 10 min. The processed cells were incubated in a cerous medium in order to precipitate H202 moieties produced by the cells. FMLP induced cell aggregation, and the H_2O_2 production was seen on the plasma membrane sites where the cells had contacted. The reaction was markedly inhibited by p-benzoquinone and ethylenediamine-tetraacetate. Aspirin, indomethacin and lidocaine, but not dexamethasone, significantly reduced cell aggregation resulting in a decrease in the number of H_2O_2 productive cells. These results indicate that FMLP-stimulated H_2O_2 production in macrophages is initiated by calcium ions and inhibited by some anti-inflammatory drugs and local anesthetics in accord with reported physiological results, and that cell-cell contact is essential to H_2O_2 production.
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