Wang Hou-Ping, He Jian, He Jian-Rong, Li Dan-Dan, Huang He, Chen Bing
Department of Anesthesia, The Second Affiliated Hospital of Chongqing Medical University, No. 74 Linjianglu, Yuzhong District, Chongqing, 400010, China.
Department of Spine Surgery, Center of Orthopedics, State Key Laboratory of Trauma and Chemical Poisoning, Daping Hospital, Army Medical University, Third Military Medical University), Chongqing, 400042, China.
Inflamm Res. 2024 Dec;73(12):2087-2107. doi: 10.1007/s00011-024-01951-z. Epub 2024 Oct 8.
This study sought to investigate the cellular and molecular alterations during the injury and recovery periods of ALI and develop effective treatments for ALI.
Pulmonary histology at 1, 3, 6, and 9 days after lipopolysaccharide administration mice were assessed. An unbiased single-cell RNA sequencing was performed in alveoli tissues from injury (day 3) and recovery (day 6) mice after lipopolysaccharide administration. The roles of Fpr2 and Dpp4 in ALI were assessed.
The most severe lung injury occurred on day 3, followed by recovery entirely on day 9 after lipopolysaccharide administration. The numbers of Il1a neutrophils, monocytes/macrophages, and Cd4 and Cd8 T cells significantly increased at day 3 after LPS administration; subsequently, the number of Il1a neutrophils greatly decreased, the numbers of monocytes/macrophages and Cd4 and Cd8 T cells continuously increased, and the number of resident alveolar macrophages significantly increased at day 6. The interactions between monocytes/macrophages and pneumocytes during the injury period were enhanced by the Cxcl10/Dpp4 pair, and inhibiting Dpp4 improved ALI significantly, while inhibiting Fpr2 did not.
Our results offer valuable insights into the cellular and molecular mechanisms underlying its progression and identify Dpp4 as an effective therapeutic target for ALI.
本研究旨在探究急性肺损伤（ALI）损伤期和恢复期的细胞及分子变化，并开发针对ALI的有效治疗方法。
评估脂多糖给药后1天、3天、6天和9天小鼠的肺组织学情况。对脂多糖给药后损伤期（第3天）和恢复期（第6天）小鼠的肺泡组织进行无偏差单细胞RNA测序。评估Fpr2和Dpp4在ALI中的作用。
脂多糖给药后第3天出现最严重的肺损伤，随后在第9天完全恢复。脂多糖给药后第3天，Il1a中性粒细胞、单核细胞/巨噬细胞以及Cd4和Cd8 T细胞数量显著增加；随后，Il1a中性粒细胞数量大幅减少，单核细胞/巨噬细胞以及Cd4和Cd8 T细胞数量持续增加，且在第6天驻留肺泡巨噬细胞数量显著增加。损伤期单核细胞/巨噬细胞与肺细胞之间的相互作用通过Cxcl10/Dpp4对增强，抑制Dpp4可显著改善ALI，而抑制Fpr2则无此效果。
我们的结果为ALI进展的细胞和分子机制提供了有价值的见解，并确定Dpp4为ALI的有效治疗靶点。
