Chest
Original ResearchDiffuse Lung DiseaseGlucose Transporter-1 Distribution in Fibrotic Lung Disease: Association With [18F]-2-Fluoro-2-Deoxyglucose-PET Scan Uptake, Inflammation, and Neovascularization
Section snippets
Subject Selection
Subjects with IPF, subjects with HPS, and healthy research volunteers were enrolled in protocols approved by the institutional review boards of the National Heart, Lung, and Blood Institute (96-H-0100) and National Human Genome Research Institute (04-HG-0211). The diagnosis of IPF was established according to published criteria.4 Subjects with HPS were diagnosed by platelet electron microscopy and genotyping; pulmonary fibrosis was diagnosed by characteristic chest CT scan findings.1 Healthy
Increased Glucose Uptake in the Lung in IPF
A subject with a history of interstitial lung disease, suggestive of IPF, underwent a PET-CT scan because of concern about possible malignancy of a small subpleural mass. The PET-CT scan showed increased FDG uptake in the regions of honeycombing and fibrosis (Figs 1A, 1B). The patient subsequently underwent a video-assisted thoracoscopic biopsy, and the pathologic diagnosis was consistent with usual interstitial pneumonia (Figs 1C, 1D). Tissue sections from this open lung biopsy were incubated
Discussion
In this report, we show that Glut-1 immunoreactivity in fibrotic lung disease localizes to erythrocytes and inflammatory cells and not fibroblasts, epithelial cells, or endothelial cells. Our data suggest that increased FDG uptake on PET scans in fibrotic lung disease is associated with Glut-1 expression by immune cells and erythrocytes and not with enhancement of the metabolic rate of epithelial cells as previously postulated.
Evidence from lung tissue and BALF cell analyses show that in
Acknowledgments
Author contributions: Drs El-Chemaly and Gochuico are the guarantors of the paper and take responsibility for the integrity of the work as a whole, from inception to published article.
Dr El-Chemaly: contributed to designing and performing the research, analyzing data, and writing the manuscript.
Dr Malide: contributed to designing and performing the research, analyzing data, and writing the manuscript.
Dr Yao: contributed to analyzing the data and revision of the manuscript.
Dr Nathan: contributed
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2022, Autoimmunity ReviewsCitation Excerpt :In ILD, it was first thought that uptake of 18F-FDG was facilitated through high expression of GLUT1–4 on macrophages, neutrophils and lymphocytes, thus reflecting inflammation [92,93]. However, it has been established that uptake of 18F-FDG reflects cell metabolism in general, and can thus also be elevated in fibrotic areas [92,93]. The non-specificity of 18F-FDG for inflammation is underlined by the fact that 18F-FDG uptake is observed from early to end-stage disease, in both clinical studies as in the animal studies that were included in this review [33,36,47,56,88].
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2022, Pharmacology and TherapeuticsCitation Excerpt :A recent study in pulmonary fibrosis mice models emphasized that pro-fibrotic alveolar macrophages were heavily dependent on glycolysis rather than OXPHOS (Xie et al., 2017). Increased expression of pulmonary glucose transporter 1 (GLUT1) and other main glycolytic mediators enabled augmented glucose consumption and downstream glycolytic pathways (El-Chemaly et al., 2013; Xie et al., 2017). Alternatively, the mitochondrial-encoded OXPHOS genes expression is decreased in alveolar macrophage from IPF patients (Tsitoura et al., 2019).
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2021, Mucosal ImmunologyCorrelation between preoperative <sup>18</sup>F-FDG PET/CT findings and postoperative short-term prognosis in lung cancer patients with idiopathic interstitial pneumonia after lung resection
2021, Respiratory InvestigationCitation Excerpt :In the present study, despite our efforts, the mechanism underlying increased glucose metabolism and the resultant high SUVmax in the IIP area remains to be clarified. El-Chemaly et al. demonstrated that increased FDG uptake on PET scans in fibrotic lung disease is associated with glucose transporter-1 expression by immune cells and erythrocytes [20]. We are also planning to perform further investigations using certain molecular biological approaches that might reveal the underlying mechanism.
Gender specific association of missense variant rs1805097 of IRS-2 and noncoding variant rs841853 of GLUT-1 genes with susceptibility to type 2 diabetes in Bangladeshi population
2020, Gene ReportsCitation Excerpt :Any malfunction in glucose transporter will affect the glucose transportation and the result will be primarily hyperglycemia that leads to diseases like diabetes mellitus. Studies also suggested that, there is an association of fibrotic lung diseases with GLUT-1 (El-Chemaly et al., 2013). Deficiency of GLUT-1 is related to neurological diseases as it is the major glucose transporter in brain.
Funding/Support: This research was supported in part by the Intramural Research Program of the National Institutes of Health (National Heart, Lung, and Blood Institute and National Human Genome Research Institute) and the National Institutes of Health [Grant 1K22HL092223, National Heart, Lung, and Blood Institute].
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