两型TNF-α的细胞毒效应与靶细胞内Ca^(2+)浓度变化的关系  

Relationship between cytotoxicity of two types of TNF-α and intracellular free calcium concentration in target cells

作　　者：石文芳[1] 尹丙姣[1] 熊平[1] 龚非力[1] 李卓娅[1] 

机构地区：[1]华中科技大学同济医学院免疫学教研室,湖北武汉430030

出　　处：《细胞与分子免疫学杂志》2004年第5期537-539,共3页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金重点项目资助 (No .39570 796)

摘　　要：目的 :比较分泌型TNF α(S TNF α)和跨膜型TNF α(TM TNF α)发挥细胞毒效应时 ,引起靶细胞内Ca2 + 浓度的变化。方法 :采用生物学活性检测法 ,观察两型TNF α对不同靶细胞的杀伤效应 ;用Fura 2检测细胞内Ca2 + 浓度的变化。结果 :TM TNF α可杀伤实验所用 6株靶细胞 ;而S TNF α则仅对其中两株有细胞毒效应。两型TNF α杀伤靶细胞时 ,均伴有明显的Ca2 + 浓度升高。用钙螯合剂EGTA(10mmol/L)预先处理靶细胞30min ,只能降低S TNF α作用的靶细胞内的Ca2 + 浓度 ,并使其细胞毒效应明显减弱 (P <0 .0 1) ;对TM TNF α无影响。结论 :两型TNF α发挥细胞毒效应时 ,均可引起靶细胞内钙离子的重分布 ,导致靶细胞内Ca2 + 浓度的升高 ,但S TNF α的作用还可能与促进胞外Ca2 +AIM: To compare the changes of free calcium concentration in target cells killed by transmembrane tumor necrosis factor-α(TM-TNF-α) and secretory TNF-α(S-TNF-α). METHODS: The cytotoxicity of two types of TNF-α was tested by bioassay. The intracellular Ca 2+ concentration was determined by Frua-2. RESULTS: TM-TNF-α had cytotoxic effect on all 6 kinds of target cells, whereas S-TNF-α could kill only two of them. The cytotoxic activity of both types of TNF-α was accompanied by a dramatically increase of intracellular free Ca 2+ concentration. The intracellular Ca 2+ concentration in the target cells treated with S-TNF-α was obviously reduced by pretreating target cells for 30 minutes with 10 μmol/L calcium chelator EGTA (P<0.01) and the cytotoxicity of S-TNF-α was significantly inhibited (P< 0.01), while the pretreatment with EGTA had no effect on the intracellular Ca 2+ concentration in the target cells treated with TM-TNF-α and the cytotoxicity of TM-TNF-α. CONCLUSION: These results suggest that both types of TNF-α increase Ca 2+ concentration in target cells by promoting the redistribution of intracellular free calcium and only S-TNF-α seems to be able to accelerate the influx of extracellular calcium into the target cells.

关 键 词：跨膜型TNF-Α 分泌型TNF-Α 细胞毒效应 CA^2+ 

分 类 号：R392.11[医药卫生—免疫学]