The effect of gliotoxin upon macrophage function.

Gliotoxin, a metabolite of the fungus Aspergillus fumigatus, inhibited phagocytosis of particulate matter by rodent macrophages. In addition, adherence to plastic surfaces by peritoneal and alveolar rodent macrophages, human peripheral blood monocytes, mouse secondary fibroblasts and L929 cells was differentially inhibited by gliotoxin. Electron microscopy which confirmed the inhibition by gliotoxin of phagocytosis of carbon particles by rodent macrophages also revealed gliotoxin-induced morphological alterations. Gliotoxin selectively affected glucose metabolism and macromolecular synthesis of rodent-derived cells and inhibited the basal rate of H2O2 production by human polymorphonuclear neutrophils; bactericidal activity of resident peritoneal macrophages was also abrogated. These gliotoxin-induced changes in cell function and metabolism occurred at concentrations well below generalized toxic levels.