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目的研究转移程度不同的小鼠肝癌细胞株对腹腔巨噬细胞功能的影响。方法在两株转移程度不同的小鼠腹水型肝癌模型中,取荷瘤小鼠腹腔巨噬细胞,检测其在干扰素γ(IFN-γ)和脂多糖(LPS)刺激下产生一氧化碳(NO)和肿瘤坏死因子α(TNF-α)的水平,并检测其活化后的杀伤能力。进一步采用夹心酶联免疫吸附测定(ELISA)方法,研究不同荷瘤小鼠腹水中IFN-γ与转化生长因子β1(TGF-β1)的水平,并用相应抗体封闭TGF-β1后,检测活化巨噬细胞产生NO能力及杀伤活性。结果经IFN-γ和LPS活化后,荷瘤小鼠腹腔巨噬细胞分泌NO和TNF-α能力明显低于正常巨噬细胞,杀伤能力下降。高转移性肝癌小鼠巨噬细胞分泌NO水平和杀伤能力均低于低转移性小鼠,但其分泌TNF-α量较高。此外,荷瘤小鼠腹水含较高水平IFN-γ与TGF-β1,不同转移程度荷瘤小鼠IFN-γ水平接近,但高转移性肝癌小鼠腹水含更多TGF-β1,而且TGF-β1的封闭可导致与肿瘤细胞共培养的巨噬细胞分泌NO的能力部分恢复。结论肿瘤细胞可以通过分泌TGF-β1等抑制性因子下调巨噬细胞的活性和免疫功能。肿瘤的转移程度可能与其分泌免疫抑制因子的能力相关。
Objective To investigate the effect of mouse hepatoma cell lines with different metastasis on the function of peritoneal macrophages. Methods Peritoneal macrophages from mice bearing tumor-bearing mice were treated with IFN-γ and lipopolysaccharide (LPS) in two models of mouse ascites hepatocellular carcinoma with different degree of metastasis. And tumor necrosis factor alpha (TNF-alpha) levels, and test its activation of the killing capacity. The levels of IFN-γ and TGF-β1 in ascites of different tumor-bearing mice were further studied by sandwich enzyme-linked immunosorbent assay (ELISA). After blocking TGF-β1 with corresponding antibodies, the activated macrophages Cells produce NO ability and killing activity. Results After activated by IFN-γ and LPS, the ability of tumor-bearing mice peritoneal macrophages to secrete NO and TNF-α was significantly lower than that of normal macrophages, and their cytotoxicity decreased. The macrophages secreting high levels of NO and the cytotoxicity of mice with high metastatic HCC were lower than those of mice with low metastasis, but secreting high levels of TNF-α. In addition, ascites in tumor-bearing mice contained higher levels of IFN-γ and TGF-β1, and IFN-γ levels were similar in tumor-bearing mice with different degrees of metastasis. However, TGF-β1 was found in ascites of mice with HCC, Blocking of β1 results in the partial recovery of the ability of macrophages co-cultured with tumor cells to secrete NO. Conclusion Tumor cells can down-regulate the activity and immune function of macrophages through the secretion of inhibitory factors such as TGF-β1. The degree of tumor metastasis may be related to its ability to secrete immunosuppressive factors.