PLC 和 PAD2 调节细胞外触发的巨细胞的释放 细胞外DNA陷
Neha Mishra1, Magdalena Mohs1, Nico Wittmann2
1Section of Rheumatology, Department of Medicine A, University Medicine Greifswald, Greifswald, Germany.
European journal of immunology
|April 2, 2025
概括
激活的人类巨细胞释放含有抗菌蛋白和炎症组分的细胞外DNA陷 (MET). 这些METs表现出强大的杀菌活性,独立于细胞分裂,为天生的免疫提供了新的见解.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 巨细胞通过炎症体和细胞外陷 (ETs) 对抗病原体.
- 中性细胞ETosis研究得很好,但巨细胞ETosis (METosis) 的理解较少.
- 转基因发生涉及DNA释放,炎症酶激活,以及潜在的感染和自身免疫作用.
研究的目的:
- 研究人类单细胞衍生巨细胞 (hMDMs) 中METosis的机制和功能.
- 确定细胞外和炎症酶激活在MET释放中的作用.
- 评估由hMDMs产生的METs的杀菌活性.
主要方法:
- 使用m-CSF和gm-CSF将hMDM区分开来.
- 使用细胞外和LPS诱导了METosis.
- 分析包括DNA,骨髓氧化酶 (MPO),素基因素,ASC斑点和IL-1β.
- 测量了对大肠杆菌的杀菌活性.
- 使用了脂酶C的抑制剂,丁氨酸脱敏酶-2和NLRP3炎症酶 (MCC950) 的抑制剂.
- 用尼卡拉金测试了血稳定性的方法.
主要成果:
- 细胞外和LPS诱导了hMDM中的MET释放,其特征是DNA,MPO,素基因组,ASC斑点和IL-1ß.
- gm-CSF分化的巨体表达MMP12并释放具有比m-CSF分化的巨体更高的杀菌活性的MET.
- MET释放取决于脂酶C,丁氨酸减小酶-2和NLRP3炎症酶的激活.
- 普尼卡拉通过稳定血膜来阻断MET释放.
- 释放的MET杀死了大肠杆菌,独立于hMDM细胞化.
结论:
- 细胞外激活的hMDMs释放基于DNA的METs,具有强大的抗菌特性.
- 转化与NLRP3炎症酶激活有关,并涉及特定的酶途径.
- 激活的METosis代表了一个重要的先天免疫机制,对自身免疫有影响.
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