Higashi N, Taki H, Nishimura Y, Higuchi M, Osawa T
Division of Chemical Toxicology and Immunochemistry, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Cell Immunol. 1993 Sep;150(2):333-42. doi: 10.1006/cimm.1993.1201.
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.
通过测量预先标记的靶细胞中51Cr和[3H]TdR的释放来研究人活化巨噬细胞的细胞毒性特性。巨噬细胞介导的细胞毒性的动力学研究表明，51Cr和[3H]TdR的释放呈现出明显的时间进程。接下来，当将[3H]TdR释放作为细胞毒性的参数进行测量时，用放线菌素D或依米丁预处理活化巨噬细胞会以剂量依赖性方式显著降低其细胞毒性。相反，用这些抑制剂预处理对51Cr释放几乎没有影响。此外，在测定培养基中添加Zn2+会导致靶细胞[3H]TdR释放减少，但不会导致51Cr释放减少。综上所述，我们的研究结果表明，靶细胞中51Cr和[3H]TdR的释放是由活化巨噬细胞通过不同的细胞毒性机制诱导的；前者在共培养过程中不需要巨噬细胞中的RNA和蛋白质合成，而后者需要。我们的研究结果还表明，巨噬细胞衍生的核酸酶可能在诱导靶细胞[3H]TdR释放中起重要作用。
