持续的中性恋性炎症与利拉辛氧化物在肺中的延迟毒性有关
Nilda C Sanchez1, Gopikrishnan Mani1, Joanna I Nowak1
1Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Scientific reports
|April 8, 2025
概括
氨酸氧化物 (PAO) 导致急性肺损伤和延迟呼吸道改造. 这种毒性涉及中性粒细胞产生中性粒细胞外细胞陷 (NETs) 和IL-33,导致持续的炎症和纤维化.
科学领域:
- 毒理学 毒理学 毒理学
- 肺部医学 肺部医学
- 化学武器制剂 化学武器制剂 化学武器制剂
背景情况:
- 甲氧化物 (PAO) 是一种带有化学战和环境污染潜力的水泡剂.
- 众所周知,PAO诱导的皮肤灼伤会导致急性器官损伤,特别是肺部.
- 延迟PAO毒性背后的机制在很大程度上仍未确定.
研究的目的:
- 研究通过皮肤暴露氧化 (PAO) 后延迟肺毒性的机制.
- 阐明中性粒细胞和相关介质在PAO诱导的气道改造中的作用.
主要方法:
- 在小鼠模型中诱导PAO在皮肤上的烧伤.
- 在暴露后6小时和24小时评估急性肺损伤.
- 暴露后10周对气道改造的评估.
- 分析中性粒细胞的流入,中性粒细胞外细胞陷 (NETs) 的形成,以及IL-33的表达.
主要成果:
- 一次皮肤PAO暴露引起了急性炎症性肺损伤.
- 急性损伤在1周后消失,但在10周后观察到有显著的呼吸道重塑.
- 长期的毒性与中性粒细胞的流入和NETs的产生有关.
- NETs和IL-33表达之间的交叉连接与周围支气管纤维化发展相关.
结论:
- 皮肤接触PAO会触发肺部最初的急性炎症阶段.
- 延迟的毒性和气道重塑是由涉及NET和IL-33的前信号循环介导的.
- 这种NETs/IL-33通路促进持续的中性粒细胞招募和NETs形成,最终导致肺纤维化.
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