Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution.
Bangwei LuoJinsong WangZongwei LiuZigang ShenRongchen ShiYu-Qi LiuYu LiuMan JiangYuzhang WuZhi-Ren ZhangPublished in: Nature communications (2016)
Inflammation resolution is an active process, the failure of which causes uncontrolled inflammation which underlies many chronic diseases. Therefore, endogenous pathways that regulate inflammation resolution are fundamental and of wide interest. Here, we demonstrate that phagocyte respiratory burst-induced hypoxia activates macrophage erythropoietin signalling to promote acute inflammation resolution. This signalling is activated following acute but not chronic inflammation. Pharmacological or genetical inhibition of the respiratory burst suppresses hypoxia and macrophage erythropoietin signalling. Macrophage-specific erythropoietin receptor-deficient mice and chronic granulomatous disease (CGD) mice, which lack the capacity for respiratory burst, display impaired inflammation resolution, and exogenous erythropoietin enhances this resolution in WT and CGD mice. Mechanistically, erythropoietin increases macrophage engulfment of apoptotic neutrophils via PPARγ, promotes macrophage removal of debris and enhances macrophage migration to draining lymph nodes. Together, our results provide evidences of an endogenous pathway that regulates inflammation resolution, with important implications for treating inflammatory conditions.
Keyphrases
- oxidative stress
- adipose tissue
- single molecule
- liver failure
- lymph node
- recombinant human
- high frequency
- signaling pathway
- cell death
- endothelial cells
- respiratory failure
- insulin resistance
- intensive care unit
- diabetic rats
- idiopathic pulmonary fibrosis
- acute respiratory distress syndrome
- systemic sclerosis
- respiratory tract
- high fat diet induced
- mechanical ventilation
- locally advanced