Macrophage-mediated cytotoxicity: role of a soluble macrophage cytotoxic factor similar to lymphotoxin and tumor necrosis factor.
Macrophage-mediated cytotoxicity: role of a soluble macrophage cytotoxic factor similar to lymphotoxin and tumor necrosis factor.
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巨噬细胞介导的细胞毒性：可溶性巨噬细胞细胞毒性因子的作用类似于淋巴毒素和肿瘤坏死因子。
DOI：
10.1073/pnas.80.20.6341
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发表时间：
1983
影响因子：
11.1
通讯作者：
Shin,HS
中科院分区：
文献类型：
--
作者：
Zacharchuk,CM;Drysdale,BE;Mayer,MM;Shin,HS
当豚鼠腹腔巨噬细胞被钙离子载体A23187或脂多糖激活产生细胞毒性时，产生不被过氧化氢酶或蛋白酶抑制剂阻断的细胞毒性因子[巨噬细胞细胞毒性因子（M phi-CF）]。通过凝胶过滤对含有M phi-CF的培养物上清液进行分级，显示了一个Mr约为45，000的细胞毒活性峰，与豚鼠光毒素（LT）相同。制备的抗纯化豚鼠LT的抗血清完全中和M phi-CF的细胞毒活性。此外，豚鼠肿瘤坏死血清中的细胞毒性因子被发现具有45，000的Mr，并且被抗LT中和。因此，M phi-CF在物理化学和免疫化学上与LT和肿瘤坏死因子相似，如果不相同的话。为了研究M phi-CF在巨噬细胞介导的细胞毒性中的作用，在添加L-929靶细胞之前，将抗LT添加到A23187或脂多糖激活的巨噬细胞中。在16个实验中的10个中，对巨噬细胞介导的细胞毒性的抑制为100%。在其他的，细胞毒性被部分阻断，最低抑制率为49%。抑制的有效性似乎与巨噬细胞活化的强度呈负相关。这些结果表明M phi-CF在巨噬细胞介导的细胞毒性中起重要作用，但不能排除另一种机制的参与。
Guinea pig peritoneal macrophages, when activated for cytotoxicity by the calcium ionophore A23187 or lipopolysaccharide, produce a cytotoxic factor [macrophage cytotoxic factor (M phi-CF)] that is not blocked by catalase or protease inhibitors. Fractionation of culture supernates containing M phi-CF by gel filtration revealed one peak of cytotoxic activity of Mr approximately 45,000, the same as guinea pig lymphotoxin (LT). Antiserum prepared against purified guinea pig LT completely neutralized the cytotoxic activity of M phi-CF. In addition, the cytotoxic factor in guinea pig tumor necrosis serum was found to have a Mr of 45,000 and was neutralized by anti-LT. Thus, M phi-CF is physicochemically and immunochemically similar to LT and tumor necrosis factor, if not identical. To investigate the role of M phi-CF in macrophage-mediated cytotoxicity, anti-LT was added to A23187- or lipopolysaccharide-activated macrophages before addition of L-929 target cells. In 10 of 16 experiments, the inhibition of macrophage-mediated cytotoxicity was 100%. In the others, cytotoxicity was blocked partially, the lowest inhibition being 49%. The effectiveness of inhibition appeared to be inversely related to the intensity of macrophage activation. These results indicate that M phi-CF plays a significant role in macrophage-mediated cytotoxicity but involvement of another mechanism cannot be excluded.