一种非分泌细胞表面突变的瘤亡因子 (TNF) 通过细胞间接触杀死细胞
1Department of Molecular Biology, Cetus Corporation, Emeryville, California 94608.
Cell
|October 19, 1990
概括
瘤亡因子 (TNF) 有两种形式:分泌和跨膜. 跨膜形式的TNF通过细胞接触直接杀死细胞,与分泌形式不同.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 瘤亡因子 (TNF) 参与瘤回归和各种病理,如败血性休克和类风湿性关节炎.
- TNF存在两种主要形式:一种17kd的分泌成分和一种26kd的跨膜形式.
- 这些TNF形式的独特生物活动尚未完全理解.
研究的目的:
- 为了研究TNF的26kd跨膜形式的生物活性.
- 为了比较跨膜TNF与分泌TNF的细胞功能.
- 为了确定TNF是否需要内部化来发挥其细胞毒性作用.
主要方法:
- 产生TNF的不可食用和仅可分泌的突变物.
- 研究这些工程TNF突变体的生物活动.
- 评估TNF对瘤和病毒感染细胞的细胞毒性作用.
主要成果:
- 26kd跨膜TNF的一个不可食用的突变有效地通过直接的细胞对细胞接触杀死目标细胞.
- 目标细胞不需要内化TNF来诱导细胞死亡.
- 跨膜形式的TNF调解局部细胞毒性.
结论:
- 与分泌成分相比,TNF的26kd整体跨膜形式具有明显的生物活性.
- 跨膜TNF可能在体内发挥作用,用于局部杀死瘤细胞和其他点.
- 这种局部作用与观察到的TNF的分泌形式的全身生物活性形成鲜明对比.
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