Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin
Many chronic inflammatory conditions are mediated by an increase in the number of monocytes in peripheral circulation, differentiation of monocytes to macrophages, and different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury. When hepcidin secretion is stimulated...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/4036 |
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| author | Praveen S. B. Dassanayake Rahil Prajapati Neil Gelman R. Terry Thompson Frank S. Prato Donna E. Goldhawk |
| author_facet | Praveen S. B. Dassanayake Rahil Prajapati Neil Gelman R. Terry Thompson Frank S. Prato Donna E. Goldhawk |
| author_sort | Praveen S. B. Dassanayake |
| collection | DOAJ |
| description | Many chronic inflammatory conditions are mediated by an increase in the number of monocytes in peripheral circulation, differentiation of monocytes to macrophages, and different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury. When hepcidin secretion is stimulated during inflammation, the iron export protein ferroportin is targeted for degradation on a limited number of cell types, including monocytes and macrophages. Such changes in monocyte iron metabolism raise the possibility of non-invasively tracking the activity of these immune cells using magnetic resonance imaging (MRI). We hypothesized that hepcidin-mediated changes in monocyte iron regulation influence both cellular iron content and MRI relaxation rates. In response to varying conditions of extracellular iron supplementation, ferroportin protein levels in human THP-1 monocytes decreased two- to eightfold, consistent with paracrine/autocrine regulation of iron export. Following hepcidin treatment, ferroportin protein levels further decreased two- to fourfold. This was accompanied by an approximately twofold increase in total transverse relaxation rate, R<sub>2</sub>*, compared to non-supplemented cells. A positive correlation between total cellular iron content and R<sub>2</sub>* improved from moderate to strong in the presence of hepcidin. These findings suggest that hepcidin-mediated changes detected in monocytes using MRI could be valuable for in vivo cell tracking of inflammatory responses. |
| first_indexed | 2024-03-11T08:40:26Z |
| format | Article |
| id | doaj.art-16e52685e2104874a4c53d0bd9981cad |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:40:26Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-16e52685e2104874a4c53d0bd9981cad2023-11-16T21:08:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244403610.3390/ijms24044036Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and HepcidinPraveen S. B. Dassanayake0Rahil Prajapati1Neil Gelman2R. Terry Thompson3Frank S. Prato4Donna E. Goldhawk5Imaging Program, Lawson Health Research Institute, London, ON N6A 4V2, CanadaImaging Program, Lawson Health Research Institute, London, ON N6A 4V2, CanadaImaging Program, Lawson Health Research Institute, London, ON N6A 4V2, CanadaImaging Program, Lawson Health Research Institute, London, ON N6A 4V2, CanadaImaging Program, Lawson Health Research Institute, London, ON N6A 4V2, CanadaImaging Program, Lawson Health Research Institute, London, ON N6A 4V2, CanadaMany chronic inflammatory conditions are mediated by an increase in the number of monocytes in peripheral circulation, differentiation of monocytes to macrophages, and different macrophage subpopulations during pro- and anti-inflammatory stages of tissue injury. When hepcidin secretion is stimulated during inflammation, the iron export protein ferroportin is targeted for degradation on a limited number of cell types, including monocytes and macrophages. Such changes in monocyte iron metabolism raise the possibility of non-invasively tracking the activity of these immune cells using magnetic resonance imaging (MRI). We hypothesized that hepcidin-mediated changes in monocyte iron regulation influence both cellular iron content and MRI relaxation rates. In response to varying conditions of extracellular iron supplementation, ferroportin protein levels in human THP-1 monocytes decreased two- to eightfold, consistent with paracrine/autocrine regulation of iron export. Following hepcidin treatment, ferroportin protein levels further decreased two- to fourfold. This was accompanied by an approximately twofold increase in total transverse relaxation rate, R<sub>2</sub>*, compared to non-supplemented cells. A positive correlation between total cellular iron content and R<sub>2</sub>* improved from moderate to strong in the presence of hepcidin. These findings suggest that hepcidin-mediated changes detected in monocytes using MRI could be valuable for in vivo cell tracking of inflammatory responses.https://www.mdpi.com/1422-0067/24/4/4036magnetic resonance imagingmonocytesiron exportferroportinhepcidininflammation |
| spellingShingle | Praveen S. B. Dassanayake Rahil Prajapati Neil Gelman R. Terry Thompson Frank S. Prato Donna E. Goldhawk Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin International Journal of Molecular Sciences magnetic resonance imaging monocytes iron export ferroportin hepcidin inflammation |
| title | Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin |
| title_full | Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin |
| title_fullStr | Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin |
| title_full_unstemmed | Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin |
| title_short | Monocyte MRI Relaxation Rates Are Regulated by Extracellular Iron and Hepcidin |
| title_sort | monocyte mri relaxation rates are regulated by extracellular iron and hepcidin |
| topic | magnetic resonance imaging monocytes iron export ferroportin hepcidin inflammation |
| url | https://www.mdpi.com/1422-0067/24/4/4036 |
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