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dc.contributor.authorPorter, Linsey
dc.contributor.authorToepfner, Nicole
dc.contributor.authorBashant, Kathleen
dc.contributor.authorGuck, Jochen
dc.contributor.authorAshcroft, Margaret
dc.contributor.authorFarahi, Neda
dc.contributor.authorChilvers, Edwin
dc.date.accessioned2018-09-27T14:11:20Z
dc.date.available2018-09-27T14:11:20Z
dc.date.issued2018
dc.identifier.issn1664-3224
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/282819
dc.description.abstractImmune cells face constant changes in their microenvironment, which requires rapid metabolic adaptation. In contrast to neutrophils, which are known to rely near exclusively on glycolysis, the metabolic profile of human eosinophils has not been characterized. Here, we assess the key metabolic parameters of peripheral blood-derived human eosinophils using real-time extracellular flux analysis to measure extracellular acidification rate and oxygen consumption rate, and compare these parameters to human neutrophils. Using this methodology, we demonstrate that eosinophils and neutrophils have a similar glycolytic capacity, albeit with a minimal glycolytic reserve. However, compared to neutrophils, eosinophils exhibit significantly greater basal mitochondrial respiration, ATP-linked respiration, maximum respiratory capacity, and spare respiratory capacity. Of note, the glucose oxidation pathway is also utilized by eosinophils, something not evident in neutrophils. Furthermore, using a colorimetric enzymatic assay, we show that eosinophils have much reduced glycogen stores compared to neutrophils. We also show that physiologically relevant levels of hypoxia (PO2 3 kPa), by suppressing oxygen consumption rates, have a profound effect on basal and phorbol-myristate-acetate-stimulated eosinophil and neutrophil metabolism. Finally, we compared the metabolic profile of eosinophils purified from atopic and non-atopic subjects and show that, despite a difference in the activation status of eosinophils derived from atopic subjects, these cells exhibit comparable oxygen consumption rates upon priming with IL-5 and stimulation with fMLP. In summary, our findings show that eosinophils display far greater metabolic flexibility compared to neutrophils, with the potential to use glycolysis, glucose oxidation, and oxidative phosphorylation. This flexibility may allow eosinophils to adapt better to diverse roles in host defense, homeostasis, and immunomodulation.
dc.description.sponsorshipThis work was supported by the Biotechnology and Biological Sciences Research Council (grant number BB/H531100/1), Medical Research Council (grant number MR/J00345X/1), Alexander von-Humboldt Stiftung (Humboldt-Professorship to JG), and an ERC Starting Grant (“LightTouch”, FP7 #282060 to JG). We also thank NIHR Cambridge Biomedical Research Centre and acknowledge the support of NIHR Comprehensive Clinical Research Network.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherFrontiers Media SA
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleMetabolic Profiling of Human Eosinophils.
dc.typeArticle
prism.publicationDate2018
prism.publicationNameFront Immunol
prism.startingPage1404
prism.volume9
dc.identifier.doi10.17863/CAM.30183
dcterms.dateAccepted2018-06-06
rioxxterms.versionofrecord10.3389/fimmu.2018.01404
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-01
dc.contributor.orcidBashant, Kathleen [0000-0003-2868-892X]
dc.contributor.orcidAshcroft, Margaret [0000-0002-0066-3707]
dc.contributor.orcidChilvers, Edwin [0000-0002-4230-9677]
dc.identifier.eissn1664-3224
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idMedical Research Council (MR/J00345X/1)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
pubs.funder-project-idCambridge University Hospitals NHS Foundation Trust (CUH) (146281)
pubs.funder-project-idBiotechnology and Biological Sciences Research Council (BB/H531100/1)
cam.issuedOnline2018-06-21


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International