Influence of various antibiotics on superoxide generation by normal human neutrophils.

Among the several killing mechanisms displayed by human neutrophils, the oxidative system is the most efficient. We have studied the influence of various antibiotics on the generation of superoxide by isolated human polymorphonuclear leukocytes (PMNL) stimulated by phorbol-myristate acetate. Among the antibiotics tested, only coumermycin significantly inhibited superoxide generation; this effect was dose-related, it depended on extracellular calcium concentration and was potentiated by sub-inhibitory concentrations of calcium channel-blocking agents. Coumermycin inhibited the influx of calcium produced by the ionophore A23187 as well as directed chemotaxis in agar and the intracellular killing of a highly susceptible strain of S. aureus. These inhibitory effects required at least 15 min of preincubation of the PMNL. Coumermycin, at clinically achievable serum concentrations, significantly impaired several PMNL functions. The mechanism could be a specific or a non-specific interaction with calcium-channels.