Apoptosis-inducing membrane vesicles - A novel agent with unique properties
Apoptosis-inducing membrane vesicles - A novel agent with unique properties
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DOI：
10.1074/jbc.m107005200
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发表时间：
2001-10-26
影响因子：
4.8
通讯作者：
Ju, ST
中科院分区：
文献类型：
--
作者：
Jodo, S;Xiao, S;Ju, ST
CD 95配体（FasL）跨膜蛋白存在于活化的T细胞和免疫系统外的细胞上。众所周知，膜FasL的周转过程是由基质金属蛋白酶介导的，其产生可溶性FasL（sFasL）。在这里，我们证明，膜FasL营业额发生有效地通过释放膜囊泡。定量分析表明，该过程与FasL-3 T3细胞的sFasL释放一样有效，但对表达FasL的T细胞的效果稍差。诱导凋亡的膜囊泡显示出在FasL表达细胞和sFasL中未发现的独特性质。与sFasL不同，囊泡相关的FasL保持生物活性，杀死对表达FasL的细胞敏感的同一组靶点。与表达FasL的T细胞相反，FasL介导的囊泡杀伤不涉及LFA-1/ICAM相互作用，也不依赖于从头蛋白质合成。这些观察结果表明，FasL载体囊泡的释放有助于细胞相关的FasL的周转，但生物活性的FasL表达囊泡对细胞相关的FasL的功能的影响是不同的sFasL。
The CD95 ligand (FasL) transmembrane protein is found on activated T cells and cells outside the immune system. A well-known turnover process of membrane FasL is mediated by matrix metalloproteinase, which generates soluble FasL (sFasL). Here, we demonstrate that membrane FasL turnover occurs effectively through the release of membrane vesicles. Quantitative analysis indicates that this process is as effective as sFasL release for FasL-3T3 cells but somewhat less effective for FasL-expressing T cells. The apoptosis-inducing membrane vesicles display unique properties not found in FasL-expressing cells and sFasL. Unlike sFasL, vesicle-associated FasL remained bioactive, killing the same panel of targets that are susceptible to FasL-expressing cells. In contrast to FasL-expressing T cells, FasL-mediated killing by vesicles do not involve LFA-1/ICAM interaction and do not depend on de novo protein synthesis. These observations indicate that the release of FasL-bearing vesicles contributes to the turnover of cell-associated FasL, but the impact of the bioactive FasL-expressing vesicles on the function of cell-associated FasL is different from that of sFasL.