RvD1 ameliorates LPS-induced acute lung injury via the suppression of neutrophil infiltration by reducing CXCL2 expression and release from resident alveolar macrophages

• Published in: International immunopharmacology 2019-11, Vol.76, p.105877-105877, Article 105877
• Main Authors: Zhang, Hua-Wei, Wang, Qian, Mei, Hong-Xia, Zheng, Sheng-Xing, Ali, Abdullahi Mohamed, Wu, Qi-Xing, Ye, Yang, Xu, Hao-Ran, Xiang, Shu-Yang, Jin, Sheng-Wei
• Format: Article
• Language: English
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - immunology; Acute Lung Injury - pathology; Acute respiratory distress syndrome; Alveoli; Animal models; Animals; Chemokine CXCL2 - antagonists & inhibitors; Chemokine CXCL2 - genetics; Chemokine CXCL2 - immunology; CXCL2; Docosahexaenoic Acids - pharmacology; Docosahexaenoic Acids - therapeutic use; Infiltration; Inflammation; Inflammatory response; Injury prevention; Lipids; Lipopolysaccharides; Lipoxin A4; Lung - drug effects; Lung - immunology; Lung - pathology; Lungs; Macrophages; Macrophages, Alveolar - drug effects; Macrophages, Alveolar - immunology; Metastases; Mice, Inbred C57BL; Neutrophil Infiltration - drug effects; Neutrophils; Plasma; Resident alveolar macrophages; Resolvin D1; Respiratory distress syndrome; Respiratory therapy; Tumor necrosis factor-TNF; Tumor necrosis factor-α
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.105877

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are life-threatening critical syndromes characterized by the infiltration of a large number of inflammatory cells that lead to an excessive inflammatory response. Resolvin D1 (RvD1), an endogenous lipid mediator, is believed to have anti-inflammatory and proresolving effects. In the present study, we examined the impact of RvD1 on the pulmonary inflammatory response, neutrophil influx, and lung damage in a murine model of lipopolysaccharide (LPS)-induced ALI. Treatment with RvD1 protected mice against LPS-induced ALI, and compared to untreated mice, RvD1-treated mice exhibited significantly ameliorated lung pathological changes, decreased tumor necrosis factor-α (TNF-α) concentrations and attenuated neutrophil infiltration. In addition, treatment with RvD1 attenuated LPS-induced neutrophil infiltration via the downregulation of CXCL2 expression on resident alveolar macrophages. Finally, BOC-2, which inhibits the RvD1 receptor lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2), reversed the protective effects of RvD1. These data demonstrate that RvD1 ameliorates LPS-induced ALI via the suppression of neutrophil infiltration by an ALX/FPR2-dependent reduction in CXCL2 expression on resident alveolar macrophages. •Resolvin D1, an endogenous lipid mediator, is believed to have anti-inflammatory and proresolving effects.•RvD1 promotes inflammatory resolution of ARDS via the suppression of CXCL2 expression on resident alveolar macrophages.•The effects of RvD1 were in an ALX/FPR2-dependent manner.