Erythromycin and roxithromycin potentiate human neutrophil locomotion in vitro by inhibition of leukoattractant-activated superoxide generation and autooxidation

Erythromycin and especially roxithromycin (1.25-20 micrograms/mL) stimulated neutrophil migration in vitro. Both antibiotics selectively inhibited superoxide generation by neutrophils activated with the N-formylated leukotactic tripeptide FMLP, the calcium ionophore A23187 and the pharmacologic agent benoxaprofen, while the responses initiated by the tumor promotor PMA and opsonized zymosan were unaffected. Neutrophil autooxidation during exposure to FMLP was also decreased by both antibiotics. The antimicrobial agents did not scavenge superoxide. Likewise, the interactions of 3H]FMLP with specific receptors on neutrophils, FMLP-activated degranulation and intracellular calcium fluxes, the activity of cytosolic protein kinase C and the release of 3H]arachidonate from calcium ionophore-stimulated neutrophils were all unaffected by the antibiotics. Erythromycin and roxithromycin in particular appear to enhance neutrophil migration by an antioxidant mechanism that is not due to inhibition of transductional events involved in the activation of NADPH-oxidase or to oxidant scavenging properties.