Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission
Galectin-1 sensitizes resting human T lymphocytes to Fas (CD95)-mediated cell death via mitochondrial hyperpolarization, budding, and fission
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DOI：
10.1074/jbc.m409752200
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发表时间：
2005-02-25
影响因子：
4.8
通讯作者：
Malorni, W
中科院分区：
文献类型：
--
作者：
Matarrese, P;Tinari, A;Malorni, W
半乳糖凝集素已经成为一个新的免疫调节蛋白家族，涉及T细胞稳态。近年来的研究表明，半乳糖凝集素-1（Galectin-1，Gal-1）通过杀伤抗肿瘤效应T细胞，在肿瘤免疫逃逸中发挥重要作用。在这里，我们发现Gal-1使人静息T细胞对Fas（CD 95）/caspase-8介导的细胞死亡敏感。此外，这种蛋白质触发凋亡程序，涉及线粒体膜电位的增加和神经酰胺途径的参与。此外，Gal-1诱导线粒体聚结、出芽和分裂，伴随着分裂相关分子h-Fis和DRP-1的增加和/或重新分布。重要的是，这些变化在静息和活化的人T细胞中均被检测到，这表明Gal-1诱导的细胞死亡可能成为分析细胞死亡过程中线粒体形态发生变化的极好模型。这是Gal-1、Fas/Fas配体介导的细胞死亡和线粒体途径之间的第一个关联，为Gal-1在慢性炎症和癌症实验模型中的免疫调节特性提供了合理的基础。
Galectins have emerged as a novel family of immunoregulatory proteins implicated in T cell homeostasis. Recent studies showed that galectin-1 (Gal-1) plays a key role in tumor-immune escape by killing antitumor effector T cells. Here we found that Gal-1 sensitizes human resting T cells to Fas (CD95)/caspase-8-mediated cell death. Furthermore, this protein triggers an apoptotic program involving an increase of mitochondrial membrane potential and participation of the ceramide pathway. In addition, Gal-1 induces mitochondrial coalescence, budding, and fission accompanied by an increase and/or redistribution of fission-associated molecules h-Fis and DRP-1. Importantly, these changes are detected in both resting and activated human T cells, suggesting that Gal-1-induced cell death might become an excellent model to analyze the morphogenetic changes of mitochondria during the execution of cell death. This is the first association among Gal-1, Fas/Fas ligand-mediated cell death, and the mitochondrial pathway, providing a rational basis for the immunoregulatory properties of Gal-1 in experimental models of chronic inflammation and cancer.