Keller R
Immunology. 1974 Aug;27(2):285-98.
Analysis of the kinetics of the interaction between nonimmune activated macrophages and syngeneic tumour cells (induced in inbred DA rats by polyoma virus, dimethylbenzanthracene or methylcholanthrene) has shown that a distinctive series of events can be clearly separated. The earliest consequence of interaction detectable by objective means is a marked decrease in tumour cell proliferation as reflected in the reduction of the capacity of tumour cells to incorporate DNA precursors such as [H]thymidine. By 3—4 hours, the cytostatic effect is strongly marked, and is essentially established after 12 hours of interaction. Shrinkage, agglutination and decrease in the number of tumour cells as examples of the morphological consequences of cytostatic target cell damage accomplished by activated macrophages are rarely perceptible before 10–12 hours although the tumour cells have completely disappeared after 24–48 hours. Under the experimental conditions employed, occasional tumour cells escaped interaction with activated macrophages. The fact that such recovery of targets was fully reversed by adding further activated macrophages indicates that tumour cell revival reflects a decrease in macrophage effector functions during prolonged incubation. The possibility that some tumour cells might be resistant to macrophage effects thus seems excluded. Activated macrophages from normal and from congenitally athymic nude mice are equally effective in reducing tumour cell proliferation. Thus T lymphocytes and/or their soluble mediators are not essential for the macrophage function under investigation. Pretreatment of activated macrophages with an extensive array of metabolic inhibitors and agents known to affect distinct cellular functions yields much data but does not yet permit a simple comprehensive interpretation. However, the findings are compatible with the thesis that macrophage activation is accompanied by the or enhanced synthesis of the cytostatic principle. Once possessed of this mechanism, other basic functional capacities of macrophages, such as membrane activity, movement or endocytosis are no longer essential for the mediation of the cytostatic effects.
对非免疫激活的巨噬细胞与同基因肿瘤细胞（由多瘤病毒、二甲基苯并蒽或甲基胆蒽在近交系DA大鼠中诱导产生）之间相互作用的动力学分析表明，一系列独特的事件能够被清晰地区分开来。通过客观方法可检测到的相互作用的最早结果是肿瘤细胞增殖显著减少，这表现为肿瘤细胞摄取DNA前体如[³H]胸腺嘧啶核苷的能力降低。到3 - 4小时，细胞抑制作用非常明显，并且在相互作用12小时后基本确立。尽管肿瘤细胞在24 - 48小时后完全消失，但作为激活巨噬细胞导致的细胞抑制性靶细胞损伤的形态学后果，如肿瘤细胞的收缩、凝集和数量减少，在10 - 12小时之前很少能察觉到。在所采用的实验条件下，偶尔有肿瘤细胞逃脱与激活巨噬细胞的相互作用。通过添加更多激活巨噬细胞能完全逆转这种靶细胞恢复的事实表明，肿瘤细胞复苏反映了长时间孵育过程中巨噬细胞效应功能的降低。因此，某些肿瘤细胞可能对巨噬细胞作用具有抗性的可能性似乎被排除。来自正常小鼠和先天性无胸腺裸鼠的激活巨噬细胞在减少肿瘤细胞增殖方面同样有效。因此，T淋巴细胞和/或其可溶性介质对于所研究的巨噬细胞功能并非必不可少。用大量代谢抑制剂和已知影响不同细胞功能的试剂对激活巨噬细胞进行预处理产生了大量数据，但尚未允许进行简单的全面解释。然而研究结果与这样的论点相符，即巨噬细胞激活伴随着细胞抑制原理的合成或增强。一旦拥有这种机制，巨噬细胞的其他基本功能能力，如膜活性、运动或内吞作用，对于细胞抑制作用的介导就不再是必需的。
