Effects of diethyldithiocarbamate on activating mechanisms of neutrophils

The effects of diethyldithiocarbamate on superoxide release by rat neutrophils were investigated in a chemiluminescence study. Diethyldithiocarbamate augmented lucigenin-dependent chemiluminescence in a concentration-dependent manner and inhibited luminol-dependent chemiluminescence at concentrations of 0.1-1 microM. In contrast, after the addition of 0.1 mM diethyldithiocarbamate, the chemiluminescence was markedly enhanced. Diethyldithiocarbamate inhibited both the myeloperoxidase activity of neutrophils and the chemiluminescence generated in a cell-free horseradish peroxidase/H2O2 and H2O2/HOCl system. The increase in lucigenin-dependent chemiluminescence brought about by diethyldithiocarbamate was inhibited by H-7, ML-7, W-7, EGTA and pertussis toxin. These results suggest that diethyldithiocarbamate may stimulate O2- production by a guanosine 5'-triphosphate protein-mediated and Ca(2+)-dependent process and that the increase in O2- release by neutrophils may be dependent not only on the direct stimulation of the signal transduction pathway but also on the increase in O2- by reducing the effect of the hydroperoxide (H2O2)-myeloperoxidase system.