Gallily R, Gifford G E, Loewenstein J
Cancer Immunol Immunother. 1986;23(1):60-6. doi: 10.1007/BF00205557.
We had previously established a murine bone marrow-derived cell line, designated JBM phi 1.1, which displayed properties of normal macrophages, including the ability to perform macrophage-mediated cytolysis. It was also found that these cells could be induced by lipopolysaccharide (LPS) to produce reproducibly high levels of a cytolytic factor (CF) resembling tumor necrosis factor (TNF). This cell line was therefore selected for further studies on macrophage-mediated tumor cell lysis and CF production. Moreover, the CF production during incubation with LPS was higher in the absence of serum than in its presence, with a maximum at days 2-3 following the addition of LPS. A factor inhibitory to CF production (CIF) was detected in our laboratory in the supernatant of embryonic fibroblast cultures. We established the experimental conditions required for the optimal production and suppressive effect of CIF. High levels of CIF activity were obtained under conditions that promote fibroblast proliferation. Addition of embryonic fibroblast culture supernatant to the macrophages shortly before LPS suppressed both LPS-induced CF production and tumoricidal activity. CIF did not affect macrophage protein synthesis in the presence or absence of LPS. However, LPS-induced interleukin 1 release was partially (55%) suppressed by embryonic fibroblast culture supernatant. Our results show that CIF does not exert a general inactivating effect on the macrophages, although it may possibly affect other functions in addition to CF production and tumor cell lysis. The strong inhibition of both the latter properties further indicates that TNF-like CF is an important mediator in macrophage-mediated tumor cell lysis.
我们之前建立了一种源自小鼠骨髓的细胞系，命名为JBM phi 1.1，它表现出正常巨噬细胞的特性，包括具有进行巨噬细胞介导的细胞溶解的能力。还发现这些细胞可被脂多糖（LPS）诱导，以可重复的方式产生高水平的一种类似于肿瘤坏死因子（TNF）的细胞溶解因子（CF）。因此，选择该细胞系用于进一步研究巨噬细胞介导的肿瘤细胞裂解和CF的产生。此外，在无血清培养条件下，与LPS孵育期间CF的产生比有血清时更高，在添加LPS后第2 - 3天达到最大值。我们实验室在胚胎成纤维细胞培养上清液中检测到一种抑制CF产生的因子（CIF）。我们确定了CIF最佳产生和抑制作用所需的实验条件。在促进成纤维细胞增殖的条件下可获得高水平的CIF活性。在LPS刺激前不久将胚胎成纤维细胞培养上清液添加到巨噬细胞中，可抑制LPS诱导的CF产生和杀肿瘤活性。无论有无LPS，CIF均不影响巨噬细胞蛋白质合成。然而，胚胎成纤维细胞培养上清液可部分（55%）抑制LPS诱导的白细胞介素1释放。我们的结果表明，CIF虽然除了影响CF产生和肿瘤细胞裂解外可能还影响其他功能，但它对巨噬细胞并没有普遍的失活作用。对后两种特性的强烈抑制进一步表明，TNF样CF是巨噬细胞介导的肿瘤细胞裂解中的重要介质。
