title: Phagocyte respiratory burst activates macrophage erythropoietin signalling to promote acute inflammation resolution.
abstract: 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.
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Bangwei
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Rongchen
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Man
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Yuzhang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Basic Medicine, Institute of Immunology, Third Military Medical University of PLA, 30 Gaotanyan Main Street, Chongqing 400038, China.
authors.forename: Zhiren
authors.identifier: 0000-0002-5238-2835
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002465:Cell Movement; D004921:Erythropoietin / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047495:PPAR gamma / Q000378:metabolism; D010587:Phagocytosis; D017467:Receptors, Erythropoietin / Q000378:metabolism; D016897:Respiratory Burst; D015398:Signal Transduction
chemical_list: D047495:PPAR gamma; D017467:Receptors, Erythropoietin; D004921:Erythropoietin