EFFECTS OF DIETHYLDITHIOCARBAMATE ON ACTIVATING MECHANISMS OF NEUTROPHILS

The effects of diethyldithiocarbamate on superoxide release by rat neu rophils were investigated in a chemiluminescence study. Diethyldithioc arbamate augmented lucigenin-dependent chemiluminescence in a concentr ation-dependent manner and inhibited luminol-dependent chemiluminescen ce at concentrations of 0.1-1 muM. In contrast, after the addition of 0.1 mM diethyldithiocarbamate, the chemiluminescence was markedly enha nced. Diethyldithiocarbamate inhibited both the myeloperoxidase activi ty of neutrophils and the chemiluminescence generated in a cell-free h orseradish peroxidase/H2O2 and H2O2/HOCl system. The increase in lucig enin-dependent chemiluminescence brought about by diethyldithiocarbama te was inhibited by H-7, ML-7, W-7, EGTA and pertussis toxin. These re sults suggest that diethyldithiocarbamate may stimulate O2- production by a guanosine 5'-triphosphate protein-mediated and Ca2+-dependent pr ocess and that the increase in O2- release by neutrophils may be depen dent not only on the direct stimulation of the signal transduction pat hway but also on the increase in O2- by reducing the effect of the hyd roperoxide (H2O2)-myeloperoxidase system.