利用质谱法解锁纳米粒子诱导的炎症体激活机制
Govind Gupta1, Jasreen Kaur1, Kunal Bhattacharya1
1Institute of Environmental Medicine, Karolinska Institutet, 171 77 Stockholm, Sweden.
ACS nano
|August 29, 2023
概括
无形二氧化纳米颗粒通过激活NLRP3炎症体并引起脂质过氧化,引发人类单细胞中的无菌炎症. 纳米颗粒的Silane修饰可以降低这种毒性.
科学领域:
- 免疫学 免疫学 免疫学
- 材料科学 材料科学 材料科学
- 毒理学 毒理学 毒理学
背景情况:
- 纳米粒子 (NP) 可以诱导无菌炎症,但分子机制尚不清楚.
- 人体单细胞特别容易受到无形二氧化NP的影响,导致炎症反应.
研究的目的:
- 为了阐明参与NP诱导无菌炎症的信号通路.
- 研究脂质代谢和炎症酶激活在单细胞对二氧化NP的反应中的作用.
主要方法:
- 通过飞行时间 (CyToF) 进行单细胞分析.
- 纳米级二次离子质谱 (nanoSIMS) 和传输电子显微镜 (TEM) 用于细胞吸收研究.
- 飞行时间二次离子质谱 (ToF-SIMS) 用于脂质分析.
- 评估炎症酶激活和细胞死亡机制.
主要成果:
- 无形二氧化NP诱导了人类单细胞中的无菌炎症和NLRP3炎症酶激活.
- 对NP的Silane修改减弱了它们的毒性.
- 暴露于NP导致脂质滴积累,并改变了血膜脂质,特别是酸丁胆 (PC).
- Lysophosphatidylcholine (LPC) 已成为炎症酶激活的关键信号分子.
- 细胞死亡通过一种非亡的,依赖脂质过氧化的途径发生.
结论:
- 基NP通过脂质信号通路激活单细胞中的NLRP3炎症体.
- 脂质过氧化会调解NP诱导的细胞死亡,从而导致无菌炎症.
- 了解这些机制对于NP的安全性和治疗应用至关重要.
关键词:
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