核细胞依赖的线粒体DNA释放与炎症性肠病中的细胞外陷形成有关
Broc Drury1, Cher S Chuah1, Rebecca Hall1
1Edinburgh IBD Science Unit, Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.
炎症性肠病 (IBD) 涉及线粒体DNA (mtDNA) 从中性粒细胞通过中性粒细胞外细胞陷 (NET) 释放. 然而,过度的系统性NET形成并不是IBD的主要驱动因素.
科学领域:
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
- 胃肠病学 胃肠病学
背景情况:
- 炎症性肠病 (IBD) 与高循环损伤相关的分子模式有关,特别是亲炎性线粒体DNA (mtDNA).
- 中性粒细胞通过中性粒细胞外细胞陷 (NET) 形成和线粒体NETosis释放mtDNA的关键作用.
研究的目的:
- 研究各种刺激,包括IBD血,诱导人体中性粒细胞的NET形成和mtDNA释放的能力.
- 评估在活跃IBD的患者中增加NET形成的证据.
主要方法:
- 人类血液中性粒细胞被刺激了A23187,粒细胞巨细胞刺激因子 (GM-CSF),脂多糖 (LPS) 和IBD患者的血.
- 量化了NET形成,线粒体NETosis以及mtDNA和总DNA的释放.
- 在血和便中测量了CitH3 (一种NET生物标志物) 的水平.
主要成果:
- NET形成显著增加了DNA和mtDNA释放,NET含有高mtDNA水平.
- GM-CSF + LPS诱导了一些mtDNA释放,但不是线粒体NETosis;单独的LPS诱导了没有NETs的DNA释放.
- 与缓解血相比,活性IBD血没有显著增加NET或mtDNA释放;在活性IBD血和便中,CitH3水平较低,与calprotectin相反相关.
结论:
- 血液中性粒细胞是通过NET形成和激活循环mtDNA的来源.
- 这项研究不支持过度的系统性NET形成作为IBD中占主导地位的病理生物学过程.
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