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Find similar grantsMolecular phenotyping of Alveolar macrophage metabolism is sponsored by University Hospitals Birmingham NHS Foundation Trust. Research on the metabolic profiling of alveolar macrophages to understand their role in lung diseases.
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The lung environment controls alveolar macrophage metabolism and responsiveness in type 2 inflammation Fine control of macrophage activation is needed to prevent inflammatory disease, particularly at barrier sites such as the lungs. However, the dominant mechanisms that regulate the activation of pulmonary macrophages during inflammation are poorly understood.
We found that alveolar macrophages (AlvMs) were much less able to respond to the canonical type 2 cytokine IL-4, which underpins allergic disease and parasitic worm infections, than macrophages from lung tissue or the peritoneal cavity.
We found that the hyporesponsiveness of AlvMs to IL-4 depended upon the lung environment but was independent of the host microbiota or the lung extracellular matrix components surfactant protein D (SP-D) and mucin 5b (Muc5b). AlvMs showed severely dysregulated metabolism relative to that of cavity macrophages. After removal from the lungs, AlvMs regained responsiveness to IL-4 in a glycolysis-dependent manner.
Thus, impaired glycolysis in the pulmonary niche regulates AlvM responsiveness during type 2 inflammation. Research Support, N. I.
H.
, Extramural Research Support, Non-U.S. Gov't Inflammation / immunology* Inflammation / metabolism Interleukin-4 / immunology Interleukin-4 / metabolism Macrophage Activation / genetics Macrophage Activation / immunology* Macrophages, Alveolar / immunology* Macrophages, Alveolar / metabolism Macrophages, Alveolar / parasitology Nippostrongylus / immunology Nippostrongylus / physiology Pulmonary Surfactant-Associated Protein D / genetics Pulmonary Surfactant-Associated Protein D / immunology Pulmonary Surfactant-Associated Protein D / metabolism Strongylida Infections / genetics Strongylida Infections / immunology Strongylida Infections / parasitology Pulmonary Surfactant-Associated Protein D MR/P026907/1/MRC_/Medical Research Council/United Kingdom MRF-009-0002-RG-SUTHE/MRF_/MRF_/United Kingdom 210661/Z/18/Z/WT_/Wellcome Trust/United Kingdom HL130938 /NH/NIH HHS/United States R01 HL080396/HL/NHLBI NIH HHS/United States R35 HL140039/HL/NHLBI NIH HHS/United States HL080396 /NH/NIH HHS/United States 202865/Z/16/Z/WT_/Wellcome Trust/United Kingdom R01 HL130938/HL/NHLBI NIH HHS/United States
According to the current listing, eligibility includes: Researchers at University Hospitals Birmingham. Confirm the full requirements in the official notice before applying.
Molecular phenotyping of Alveolar macrophage metabolism is funded by University Hospitals Birmingham NHS Foundation Trust. Verify program details on the funder's official page before applying.
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