T细胞亡对过度活化的中性粒细胞 delivered-NETs-MPO/NE复合体更容易受到影响
Cheng Lu1, Lifei Shao1, Heyue Li1
1Research Center for Neutrophil Engineering Technology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou 215002, Jiangsu Province, China.
中性粒细胞外细胞陷 (NETs) 含有髓氧化酶 (MPO) 和中性粒细胞弹性酶 (NE) 诱导T细胞死亡在败血症. 抑制NET或转移线粒体可能会带来治疗效益.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 病理生理学 病理生理学
背景情况:
- 败血症涉及免疫细胞失调,特别是在多态核白细胞 (PMN) 和T细胞之间.
- 中性细胞细胞外陷 (NETs) 和它们的酶与败血症的发病有关,但T细胞亡的机制尚不清楚.
研究的目的:
- 阐明NETs衍生蛋白酶 (MPO,NE) 诱导T细胞亡的机制.
- 研究线粒体转移在保护T细胞免受NET诱导的亡中的作用.
主要方法:
- 与T细胞一起培养Phorbol 12-myristate 13-acetate (PMA) 激活的PMN.
- 评估NETs的形成,T细胞亡,增殖,耗尽,DNA损伤和线粒体功能.
- 流式细胞计,电子显微镜,免疫光学,分子检测,以及在LPS挑战小鼠体内验证.
主要成果:
- 通过PMA激活的PMN释放NETs-MPO/NE复合体,诱导T细胞亡.
- 核转位的MPO/NE导致DNA双链断裂和线粒体功能障碍,激活内在亡.
- NETs降解 (DNase I) 或蛋白酶抑制降低了T细胞亡.
- 从静止的PMN转移线粒体部分恢复了T细胞功能,并减少了细胞亡.
结论:
- 由NETs衍生的MPO/NE通过DNA损伤和线粒体功能障碍驱动T细胞亡.
- NETs清除,蛋白酶抑制和线粒体转移代表了因败血症引起的T细胞亡的潜在治疗策略.
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