Stimulation of human and canine neutrophil metabolism by amphotericin B

Abstract

The effect of an antifungal agent, amphotericin B, on human and canine neutrophil metabolism was studied. Commercial preparations of amphotericin B in concentrations ranging from 5 to 100 micrograms/ml stimulated neutrophil chemiluminescence in the presence of 10(-8) M luminol. This response was blocked by 2-deoxyglucose, a metabolic inhibitor, and by the absence of extracellular calcium ions. Neither pure amphotericin B nor the solubilizing agent present in the commercial preparation, alone or in combination, stimulated neutrophil chemiluminescence. Commercial amphotericin B caused an increase in oxygen uptake by neutrophils but no detectable superoxide anion production. Neutrophils were injured by commercial amphotericin B, as shown by an increase in trypan blue dye uptake but not cell lysis. Binding of amphotericin B to neutrophil membrane sterol with a subsequent alteration in membrane configuration is the most likely cause of metabolic stimulation.