【摘要】 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。更多还原

【Abstract】 Objective To explore the effect on immunological roles of peritoneal macrophages caused by murine hepatoma cells with different metastatic ability. Methods Peritoneal macrophages were isolated from mice bearing with different metastatic ascites hepatoma cells.The levels of nitric oxide(NO) and tumor necrosis factor-α(TNF-α) from macrophages stimulated with lipopolysaccharide(LPS) and interferon-γ(IFN-γ) were analyzed,and the cytotoxicity activity of the macrophages was evaluated.In addition,expressions of TFN-γ and transforming growth factor-betal(TGF-β1) were measured by sandwich ELISA in the ascites of mice bearing tumors.Then,anti-TGF-β1 antibody was added to the co-culture,and its effect on the expression of NO and cytotoxic ability of peritoneal macrophages examined.Results Compared with those from normal mice,the macrophages from mice bearing ascites hepatoma produced significantly less NO and TNF-α when they were activated with LPS and IFN-γ,and the cytotoxic ability also decreased.Both NO expression and the cytotoxic ability of the macrophages from mice with higher mestastic hepatoma were less than those from mice with lower metastasitic hepatoma,but the level of TNF-α of the former was higher.Moreover,abundant IFN-γ and TGF-β1 were detected in the ascites.Although there was no obvious difference in the production of IFN-γ between mice with different hepatomas,the level of TGF-β1 was much higher in the mice with higher metastasitic hepatoma.Finally,the blocking with anti-TGF-β1 in the co-culture rescued partly the production of NO of the macrophages.Conclusion Activity and immunological function of macrophages can be decreased by tumor cells via the production of suppressants-like TGF-β1,and the metastatic ability of tumors might be correlated with their ability to secrete immunosuppressants.更多还原