Acute respiratory distress syndrome (ARDS) is a fatal disease characterized by excessive infiltration of inflammatory cells. MCTR1 is an endogenously pro‐resolution lipid mediator. We tested the hypothesis that MCTR1 accelerates inflammation resolution through resident M2 alveolar macrophage polarization. The mice received MCTR1 via intraperitoneal administration 3 days after LPS stimulation, and then, the bronchoalveolar lavage (BAL) fluid was collected 24 hours later to measure the neutrophil numbers. Flow cytometry was used to sort the resident and recruited macrophages. Post‐treatment with MCTR1 offered dramatic benefits in the resolution phase of LPS‐induced lung injury, including decreased neutrophil numbers, reduced BAL fluid protein and albumin concentrations and reduced histological injury. In addition, the expression of the M2 markers Arg1, FIZZ1, Remlα, CD206 and Dectin‐1 was increased on resident macrophages in the LPS + MCTR1 group. Resident macrophage depletion abrogated the therapeutic effects of MCTR1, and reinjection of the sorted resident macrophages into the lung decreased neutrophil numbers. Finally, treatment with MCTR1 increased STAT6 phosphorylation. The STAT6 inhibitor AS1517499 abolished the beneficial effects of MCTR1. In conclusion, MCTR1 promotes resident M2 alveolar macrophage polarization via the STAT6 pathway to accelerate resolution of LPS‐induced lung injury.

中文翻译：

---

MCTR1通过STAT6介导的小鼠M2肺泡巨噬细胞驻留极化增强脂多糖诱导的肺损伤的缓解。

急性呼吸窘迫综合征（ARDS）是一种致命疾病，其特征在于炎症细胞过度浸润。MCTR1是内源性的高分辨率脂质介体。我们测试了MCTR1通过驻留的M2肺泡巨噬细胞极化促进炎症消退的假说。在LPS刺激3天后，通过腹膜内给予小鼠MCTR1，然后在24小时后收集支气管肺泡灌洗液（BAL），以测量中性粒细胞数量。流式细胞仪用于分类常驻和募集的巨噬细胞。MCTR1的后处理在LPS诱发的肺损伤的缓解阶段提供了巨大的益处，包括减少中性粒细胞数量，减少BAL液蛋白和白蛋白浓度以及减少组织损伤。此外，LPS + MCTR1组中常驻巨噬细胞的M2标记Arg1，FIZZ1，Remlα，CD206和Dectin-1的表达增加。居民巨噬细胞耗竭废止了MCTR1的治疗作用，并将分类的居民巨噬细胞重新注入肺部可减少中性粒细胞数量。最后，用MCTR1处理可增加STAT6磷酸化。STAT6抑制剂AS1517499废除了MCTR1的有益作用。总之，MCTR1通过STAT6途径促进常驻M2肺泡巨噬细胞极化，以加速LPS诱导的肺损伤的缓解。最后，用MCTR1处理可增加STAT6磷酸化。STAT6抑制剂AS1517499废除了MCTR1的有益作用。总之，MCTR1通过STAT6途径促进常驻M2肺泡巨噬细胞极化，以加速LPS诱导的肺损伤的缓解。最后，用MCTR1处理可增加STAT6磷酸化。STAT6抑制剂AS1517499废除了MCTR1的有益作用。总之，MCTR1通过STAT6途径促进常驻M2肺泡巨噬细胞极化，以加速LPS诱导的肺损伤的缓解。