MCTR1 enhances the resolution of lipopolysaccharide‐induced lung injury through STAT6‐mediated resident M2 alveolar macrophage polarization in mice

Autor: Yang Ye, Shengwei Jin, Zhang Huawei, Fang-gao Smith, Hong-Xia Mei, Qian Wang, Shengxing Zheng, Hao-Ran Xu, Shu-Yang Xiang, Qian Yang
Rok vydání: 2020
Předmět:
Lipopolysaccharides
0301 basic medicine
ARDS
Lipopolysaccharide
Neutrophils
Acute Lung Injury
Lung injury
Flow cytometry
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
resolution phase of inflammation
Macrophages
Alveolar
medicine
Animals
Lung
STAT6
Inflammation
Oncogene Proteins
Respiratory Distress Syndrome
medicine.diagnostic_test
business.industry
lipopolysaccharide
Cell Polarity
Original Articles
Cell Biology
acute respiratory distress syndrome
Macrophage Activation
respiratory system
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Bronchoalveolar lavage
chemistry
030220 oncology & carcinogenesis
Immunology
Alveolar macrophage
Molecular Medicine
Original Article
alveolar macrophage
STAT6 Transcription Factor
business
Bronchoalveolar Lavage Fluid
MCTR1
Signal Transduction
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
DOI: 10.1111/jcmm.15481
Popis: 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.
Databáze: OpenAIRE
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