Sionov R V, Gallily R
Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Cell Immunol. 1992 Jul;142(2):416-25. doi: 10.1016/0008-8749(92)90301-5.
It is well documented that activated macrophages, but not nonactivated ones, kill tumor cells in vitro without damaging normal cells. We, however, have previously shown that embryo-derived teratocarcinoma cells (F9, P19, PCC4) are efficiently killed by nonactivated macrophages as well as by activated ones. Whereas other tumor cells are killed extracellularly by macrophages, we found that F9 teratocarcinoma cells are phagocytosed alive by macrophages and subsequently killed intracellularly by a process dependent on intact lysosomal function. Neither the H-2 antigens nor the mRNAs for the alpha-chain and beta 2-microglobulin are detectable in embryo-derived teratocarcinoma cells. An obvious explanation for this unique killing is that the nonactivated macrophages recognize and kill these cells due to their lack of class I MHC antigen expression, assuming that class I MHC gene products on the target cells switch off the cytolytic machinery of nonactivated macrophages. Our present findings demonstrate that there is no correlation between H-2 antigen expression on tumor cells and their susceptibility to killing by macrophages. Retinoic acid-differentiated F9 cells and P19 cells expressing H-2 antigen after exposure to MAF (IFN-gamma) were sensitive to the killing by nonactivated macrophages. Hybrids that arose from fusion of P19 teratocarcinoma cells with embryonal normal fibroblasts (C57BL/6), which displayed the morphology of embryonal carcinoma stem cells and expressed H-2 antigens, were also sensitive to the killing by nonactivated macrophages. On the other hand, the H-2-negative testicular 402AX teratocarcinoma cells and K1735P melanoma cells were both resistant to the killing by nonactivated macrophages. We concluded that the unique killing of embryo-derived teratocarcinoma cells by nonactivated murine macrophages is not related to a lack of H-2 antigen expression.
有充分的文献记载，活化的巨噬细胞而非未活化的巨噬细胞能在体外杀死肿瘤细胞而不损伤正常细胞。然而，我们之前已经表明，胚胎来源的畸胎瘤细胞（F9、P19、PCC4）既能被未活化的巨噬细胞有效杀死，也能被活化的巨噬细胞杀死。其他肿瘤细胞是被巨噬细胞在细胞外杀死，而我们发现F9畸胎瘤细胞被巨噬细胞活吞噬，随后通过依赖完整溶酶体功能的过程在细胞内被杀死。在胚胎来源的畸胎瘤细胞中检测不到H-2抗原以及α链和β2微球蛋白的mRNA。对于这种独特杀伤作用的一个明显解释是，未活化的巨噬细胞由于这些细胞缺乏I类MHC抗原表达而识别并杀死它们，假定靶细胞上的I类MHC基因产物关闭了未活化巨噬细胞的溶细胞机制。我们目前的研究结果表明，肿瘤细胞上H-2抗原的表达与其对巨噬细胞杀伤的敏感性之间没有相关性。维甲酸分化的F9细胞和暴露于MAF（干扰素-γ）后表达H-2抗原的P19细胞对未活化巨噬细胞的杀伤敏感。由P19畸胎瘤细胞与胚胎正常成纤维细胞（C57BL/6）融合产生的杂种细胞，其表现出胚胎癌干细胞的形态并表达H-2抗原，对未活化巨噬细胞的杀伤也敏感。另一方面，H-2阴性的睾丸402AX畸胎瘤细胞和K1735P黑色素瘤细胞对未活化巨噬细胞 的杀伤均有抗性。我们得出结论，未活化的鼠巨噬细胞对胚胎来源的畸胎瘤细胞的独特杀伤作用与缺乏H-2抗原表达无关。
