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.
Izumi
Y
Y
Department of Public Health, Yamaguchi University, School of Medicine, Ube, Japan.
Ogino
K
K
Murata
T
T
Kobayashi
H
H
Hobara
T
T
D000166:Acridines; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008163:Luminescent Measurements; D008297:Male; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
D000166:Acridines; D002121:Calcium Channel Blockers; D002147:Calmodulin; D013481:Superoxides; C033472:10,10'-dimethyl-9,9'-biacridinium; D009240:N-Formylmethionine Leucyl-Phenylalanine; D004050:Ditiocarb; D009195:Peroxidase; D011493:Protein Kinase C