GM-CSF Enhances Macrophage Glycolytic Activity in vitro and Improves Detection of Inflammation in vivoReportar como inadecuado


GM-CSF Enhances Macrophage Glycolytic Activity in vitro and Improves Detection of Inflammation in vivo


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Publication Date: 2016

Journal Title: Journal of Nuclear Medicine

Publisher: Society of Nuclear Medicine and Molecular Imaging

Language: English

Type: Article

Metadata: Show full item record

Citation: Singh, P., González-Ramos, S., Mojena, M., Rosales-Mendoza, C. E., Emami, H., Swanson, J., Morss, A., et al. (2016). GM-CSF Enhances Macrophage Glycolytic Activity in vitro and Improves Detection of Inflammation in vivo. Journal of Nuclear Medicine

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Abstract: Background. 18F-fluorodeoxyglucose (18F-FDG) accumulates in glycolytically active tissues, and is known to concentrate in tissues that are rich in activated macrophages. In this study, we test the hypotheses that human GM-CSF, a clinically used cytokine: a) increases macrophage glycolysis and deoxyglucose uptake in vitro, and b) acutely enhances 18F-FDG uptake within inflamed tissues such as atherosclerotic plaques in vivo. Methods. In vitro experiments were conducted in human macrophages whereby inflammatory activation and uptake of radiolabeled 2-deoxyglucose (2D-Glc) was assessed before and after granulocyte-macrophage colony stimulating factor (GM-CSF) exposure. In vivo studies were performed in mice and in New Zealand White rabbits to assess the effect of GM-CSF on 18F-FDG uptake in normal vs. inflamed arteries, using positron emission tomography (PET). Results. Incubation of human macrophages with GM-CSF, resulted in increased glycolysis and increased 2D-Glc uptake (p<0.05). This effect was attenuated by neutralizing antibodies against tumor necrosis factor alpha (TNF-α) or after silencing or inhibition of PFKFB3. In vivo, in mice and in rabbits, intravenous GM-CSF administration resulted in a 70% and 73% increase (p<0.01 for both, respectively) in arterial 18F-FDG uptake in atherosclerotic animals but not in non-atherosclerotic controls. Histopathologic analysis demonstrated a significant correlation between in vivo 18F-FDG uptake and macrophage staining (R=0.75, p<0.01). Conclusions. GM-CSF substantially augments glycolytic flux in vitro (via a mechanism dependent on ubiquitous type 6-phosphofructo-2-kinase and TNF-α), and increases 18F-FDG uptake within inflamed atheroma in vivo. These findings demonstrate that GM-CSF can be used to enhance detection of inflammation. Further studies should explore the role of GM-CSF stimulation to enhance the detection of inflammatory foci in other disease states.

Sponsorship: JHFR is part-supported by the Cambridge Biomedical Research Centre, the British Heart Foundation and HEFCE. ZAF is supported by NIH/NHLBI R01 HL071021, R01 HL078667; NIH/NBIB R01 EB009638 and NIH/NHLBI Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C. PS was supported by a grant from the NHLBI (5T32 HL076136), and is funded by The Marfan Foundation. LB was supported by SAF2014-52492R, IPT2012-1331-060000 from MINECO; RD12/0042/0019 and Ciberehd are funded by the Instituto de Salud Carlos III, and S2010/BMD-2378 from Comunidad de Madrid, and Dr. A Tawakol is supported by NIH/NHLBI R01 HL122177.

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This record's URL: https://www.repository.cam.ac.uk/handle/1810/254337





Autor: Singh, ParmanandGonzález-Ramos, SilviaMojena, MarinaRosales-Mendoza, César EduardoEmami, HamedSwanson, JeffreyMorss, AlexFayad,

Fuente: https://www.repository.cam.ac.uk/handle/1810/254337



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