The synthetic non-toxic drug 2,3-dimethyl-6(2-dimethylaminoethyl)-6H- indolo-(2,3-b)quinoxaline inhibits neutrophil production of reactive oxygen species

Abstract

The effects of the non-toxic drug 2,3-dimethyl-6(2-dimethylaminoethyl)- 6H-indolo-(2,3b)quinoxaline (B220) on the generation of reactive oxygen species from human neutrophils were investigated. The data show that B220 inhibits neutrophil release of reactive oxygen species, as well as intracellular generation of reactive oxygen species. The inhibition is not achieved through direct oxygen radical scavenger activity of B220, and the drug has no immediate effects on the activity of the assembled oxidase. Radical production and release were inhibited by all agonists tested [i.e. the protein kinase C-activating phorbol ester phobol myristate acetate; the receptor-specific agonist N-formylmethionyl-leucyl-phenylalanine (fMLP); and serum-opsonized yeast particles] in the presence of B220. The drug also inhibits phagocytosis and fMLP-induced mobilization of granules. However, based on the fact that the effects of B220 on phagocytosis and granule mobilization are much less significant than its effect on radical production, we suggest that the signal(s) affected by B220 is (are) located mainly downstream of the point at which the signals are generated to promote oxidase activation and phagocytosis or granule secretion, respectively.