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GM-CSF enhances macrophage glycolytic activity in vitro and improves detection of inflammation in vivo

AutorGonzález-Ramos, Silvia; Mojena, Marina; Rosales-Mendoza, César Eduardo; Paz-García, Marta; Martín-Sanz, Paloma ; Boscá, Lisardo ; Tawakol, Ahmed
Palabras claveMacrophage
Inflammation
GM-CSF
Glycolysis
18F-FDG-PET
Fecha de publicación2016
EditorSociety of Nuclear Medicine and Molecular Imaging
CitaciónJournal of Nuclear Medicine 57(9): 1428-1435 (2016)
ResumenF-FDG accumulates in glycolytically active tissues and is known to concentrate in tissues that are rich in activated macrophages. In this study, we tested the hypotheses that human granulocyte-macrophage colony-stimulating factor (GM-CSF), a clinically used cytokine, increases macrophage glycolysis and deoxyglucose uptake in vitro and acutely enhances F-FDG uptake within inflamed tissues such as atherosclerotic plaques in vivo. Methods: In vitro experiments were conducted on human macrophages whereby inflammatory activation and uptake of radiolabeled 2-deoxyglucose was assessed before and after GM-CSF exposure. In vivo studies were performed on mice and New Zealand White rabbits to assess the effect of GM-CSF on F-FDG uptake in normal versus inflamed arteries, using PET. Results: Incubation of human macrophages with GM-CSF resulted in increased glycolysis and increased 2-deoxyglucose uptake (P , 0.05). This effect was attenuated by neutralizing antibodies against tumor necrosis factor-α or after silencing or inhibition of 6-phosphofructo- 2-kinase. 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 F-FDG uptake in atherosclerotic animals but not in nonatherosclerotic controls. Histopathologic analysis demonstrated a significant correlation between in vivo F-FDG uptake and macrophage staining (R 5 0.75, P , 0.01). Conclusion: GM-CSF substantially augments glycolytic flux in vitro (via a mechanism dependent on ubiquitous type 6-phosphofructo-2-kinase and tumor necrosis factor-α) and increases F-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.
URIhttp://hdl.handle.net/10261/151001
DOI10.2967/jnumed.115.167387
Identificadoresdoi: 10.2967/jnumed.115.167387
issn: 0161-5505
e-issn: 2159-662X
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