Effects of 3-deazaadenosine on antibody-dependent cellular cytoxicity and phagocytosis: reciprocal inhibition and augmentation of these functions in various effector cell populations.
3-Deazaadenosine (3-DAA), an inhibitor of S-adenosyl-L-homocysteine hydrolase, caused a dose-dependent inhibition of antibody-dependent cellular cytotoxicity (ADCC) against erythrocyte target cells of mouse spleen effector cells and complete Freund's adjuvant-induced peritoneal exudate cells. Inhibition of ADCC was accompanied by a proportional augmentation of antibody-dependent phagocytosis (ADø). When resident peritoneal cells were used as the source of effectors, ADø was inhibited by 3-DAA without augmentation of ADCC. Long-term (overnight) preincubation studies showed that the effect of 3-DAA on peritoneal ADø increased with time and was irreversible. Peritoneal exudate cells elicited by sodium caseinate mediated both antibody-dependent and -independent (spontaneous) phagocytosis. 3-DAA was shown as a potent and irreversible inhibitor of spontaneous phagocytosis. Inhibition of phagocytosis in these cell preparations resulted in augmentation of ADCC. In most of these effector cell populations, effects of 3-DAA were potentiated by the presence of L-homocysteine thiolactone.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D001202:Ascitic Fluid / Q000166:cytology; D002645:Chickens / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D010587:Phagocytosis / Q000187:drug effects*; D012263:Ribonucleosides / Q000494:pharmacology*; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000166:cytology; D014372:Tubercidin / Q000494:pharmacology*
D012263:Ribonucleosides; C018258:3-deazaadenosine; D014372:Tubercidin