Journal of Advanced Research (Jan 2025)
RvD1 improves resident alveolar macrophage self-renewal via the ALX/MAPK14/S100A8/A9 pathway in acute respiratory distress syndrome
- Yang Ye,
- Qian Yang,
- Jinling Wei,
- Chenxi Shen,
- Haixing Wang,
- Rong Zhuang,
- Yuan Cao,
- Yajun Ding,
- Haoran Xu,
- Shuyang Xiang,
- Hongxia Mei,
- Zhongwang Li,
- Xiya Ren,
- Chen Zhang,
- Ji Xiao,
- Shengxing Zheng,
- Ting Li,
- Ruifeng Zeng,
- Huacheng Liu,
- Han Lin,
- Wangning Shang-guan,
- Ming Li,
- Shengwei Jin,
- Qian Wang
Affiliations
- Yang Ye
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Qian Yang
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Jinling Wei
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Chenxi Shen
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Haixing Wang
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Rong Zhuang
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Yuan Cao
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Yajun Ding
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Haoran Xu
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Shuyang Xiang
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Hongxia Mei
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Zhongwang Li
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Xiya Ren
- Wenzhou Medical University, Wenzhou, People’s Republic of China
- Chen Zhang
- Wenzhou Medical University, Wenzhou, People’s Republic of China
- Ji Xiao
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Shengxing Zheng
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Ting Li
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Ruifeng Zeng
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Huacheng Liu
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Han Lin
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Wangning Shang-guan
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China
- Ming Li
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China
- Shengwei Jin
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China; Corresponding authors at: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province 325027, People’s Republic of China.
- Qian Wang
- Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, People’s Republic of China; Key Laboratory of Anesthesiology of Zhejiang Province, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, People’s Republic of China; Corresponding authors at: Department of Anesthesia and Critical Care, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, Zhejiang Province 325027, People’s Republic of China.
- Journal volume & issue
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Vol. 67
pp. 289 – 299
Abstract
Introduction: Acute respiratory distress syndrome (ARDS) is a pulmonary inflammatory process primarily caused by sepsis. The resolution of inflammation is an active process involving the endogenous biosynthesis of specialized pro-resolving mediators, including resolvin D1 (RvD1). Resident alveolar macrophages (RAMs) maintain pulmonary homeostasis and play a key role in the resolution phase. However, the role of RAMs in promoting the resolution of inflammation by RvD1 is unclear. Objectives: Here, we investigated the mechanisms of RvD1 on regulating RAMs to promote the resolution of ARDS. Methods: Mice were administered lipopolysaccharide and/or Escherichia coli via aerosol inhalation to establish a self-limited ARDS model. Then, RvD1 was administered at the peak inflammatory response. RAMs self-renewal was measured by flow cytometry, RAM phagocytosis was measured by two-photon fluorescence imaging. In addition, plasma was collected from intensive care unit patients on days 0–2, 3–5, and 6–9 to measure RvD1 and S100A8/A9 levels using triple quadrupole/linear ion trap mass spectrometry. Results: RAMs were found to play a pivotal role in resolving inflammation during ARDS, and RvD1 enhanced RAM proliferation and phagocytosis, which was abrogated by a lipoxin A4 receptor (ALX, RvD1 receptor) inhibitor. Both primary RAMs transfected with rS100A8/A9 and/or S100A8/A9 siRNA and S100A9-/- mice (also deficient in S100A8 function) showed higher turnover and phagocytic function, indicating that RvD1 exerted its effects on RAMs by inhibiting S100A8/A9 production in the resolution phase. RvD1 reduced S100A8/A9 and its upstream MAPK14 levels in vivo and in vitro. Finally, in the patients, RvD1 levels were lower, but S100A8/A9 levels were higher. Conclusions: We propose that RvD1 improved RAM self-renewal and phagocytosis via the ALX/MAPK14/S100A8/A9 signaling pathway. Plasma RvD1 and S100A8/A9 levels were negatively correlated, and associated with the outcome of sepsis-induced ARDS.
