针对CD177+中性粒细胞的线粒体复合体I减轻了肺缺血-再输液损伤
Junqi Wu1, Peigen Gao1, Chenlu Yang2
1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China; Shanghai Engineering Research Center of Lung Transplantation, Shanghai, China.
Cell reports. Medicine
|May 21, 2025
概括
激活的CD177+中性粒细胞通过增加炎症和线粒体活动来驱动肺移植损伤. 准线粒体功能为初级移植功能障碍提供了潜在的治疗方法.
科学领域:
- 免疫学 免疫学 免疫学
- 移植生物学 移植生物学
- 细胞生物学 细胞生物学
背景情况:
- 主要移植功能障碍 (PGD) 是肺移植后的主要死亡原因.
- 中性粒细胞是PGD炎症过程中的关键参与者.
研究的目的:
- 为了研究参与肺缺血-再输液损伤 (IRI) 的中性粒细胞亚型.
- 确定PGD的潜在生物标志物和治疗点.
主要方法:
- 在小鼠IRI模型中使用了单细胞RNA测序和空间转录组学.
- 人类肺移植接受者被分析了潜在的生物标志物.
- 在小鼠和老鼠模型中使用IACS-010759准线粒体功能.
主要成果:
- 鉴定出CD177+中性粒细胞是活性亚种群,对肺损伤有显著的贡献.
- CD177+中性粒细胞显示氧化酸化和线粒体复合体I活性增加.
- 在人类接受者中,CD177+中性粒细胞预测了严重的PGD (AUC = 0.871).
- 针对线粒体复合体I减少了CD177+中性粒细胞的激活,并减轻了肺损伤.
结论:
- CD177+中性粒细胞是肺IRI和PGD的关键驱动因素.
- CD177+中性粒细胞作为严重PGD的早期诊断生物标志物.
- 抑制线粒体功能是PGD的一个有前途的治疗策略.
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