Chromium and tritiated thymidine releases from target cells are differential events in human monocyte/macrophage-mediated cytotoxicity.
Cytotoxic properties of human activated macrophages were investigated by measuring both 51Cr and [3H]TdR releases from prelabeled target cells. The kinetic study of macrophage-mediated cytotoxicity indicated that 51Cr and [3H]TdR releases showed a distinct time course. Next, when [3H]TdR release was measured as a parameter for cytotoxicity, pretreatment of activated macrophages with either actinomycin D or emetine remarkably decreased their cytotoxicity in a dose-dependent manner. In contrast, the pretreatment with these inhibitors had little effect on 51Cr release. Furthermore, the addition of Zn2+ in the assay medium caused the decrease in [3H]TdR release but not 51Cr release from the target cells. Taken together, our findings indicate that 51Cr and [3H]TdR releases from the target cells are induced by activated macrophages through different cytotoxic mechanisms; the former does not require RNA and protein syntheses in macrophages during coculture, whereas the latter requires them. Our findings also suggest that macrophage-derived nuclease may play an important role for inducing [3H]TdR release from the target cells.
Higashi
N
N
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Taki
H
H
Nishimura
Y
Y
Higuchi
M
M
Osawa
T
T
D002860:Chromium Radioisotopes; D003602:Cytotoxicity, Immunologic; D004247:DNA / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D004640:Emetine / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D013936:Thymidine / Q000378:metabolism*; D014316:Tritium; D015032:Zinc / Q000494:pharmacology
D002860:Chromium Radioisotopes; D014316:Tritium; D003609:Dactinomycin; D004247:DNA; D015032:Zinc; D013936:Thymidine; D004640:Emetine