Metabolic Profiling of Human Eosinophils.
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Authors
Porter, Linsey
Toepfner, Nicole
Bashant, Kathleen R
Guck, Jochen
Farahi, Neda
Chilvers, Edwin R
Publication Date
2018Journal Title
Front Immunol
ISSN
1664-3224
Publisher
Frontiers Media SA
Volume
9
Pages
1404
Language
eng
Type
Article
Physical Medium
Electronic-eCollection
Metadata
Show full item recordCitation
Porter, L., Toepfner, N., Bashant, K. R., Guck, J., Ashcroft, M., Farahi, N., & Chilvers, E. R. (2018). Metabolic Profiling of Human Eosinophils.. Front Immunol, 9 1404. https://doi.org/10.3389/fimmu.2018.01404
Abstract
Immune 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.
Keywords
atopy, eosinophil, glycolysis, hypoxia, metabolism, neutrophil, oxidative phosphorylation, real-time deformability cytometry
Sponsorship
This 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.
Funder references
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Medical Research Council (MR/J00345X/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Biotechnology and Biological Sciences Research Council (BB/H531100/1)
Identifiers
External DOI: https://doi.org/10.3389/fimmu.2018.01404
This record's URL: https://www.repository.cam.ac.uk/handle/1810/282819
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