Red Blood Cell-Derived Iron Alters Macrophage Function in COPD
Lung macrophage iron levels are increased in COPD patients. Lung macrophage iron levels are thought to be increased by cigarette smoke, but the role of red blood cells (RBCs) as a source of iron has not been investigated. We investigate RBCs as a potential source of alveolar iron in COPD, and determ...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/12/1939 |
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| author | James M. Baker Molly Hammond Josiah Dungwa Rajesh Shah Angeles Montero-Fernandez Andrew Higham Simon Lea Dave Singh |
| author_facet | James M. Baker Molly Hammond Josiah Dungwa Rajesh Shah Angeles Montero-Fernandez Andrew Higham Simon Lea Dave Singh |
| author_sort | James M. Baker |
| collection | DOAJ |
| description | Lung macrophage iron levels are increased in COPD patients. Lung macrophage iron levels are thought to be increased by cigarette smoke, but the role of red blood cells (RBCs) as a source of iron has not been investigated. We investigate RBCs as a potential source of alveolar iron in COPD, and determine the effect of RBC-derived iron on macrophage function. We used lung tissue sections to assess RBC coverage of the alveolar space, iron and ferritin levels in 11 non-smokers (NS), 15 smokers (S) and 32 COPD patients. Lung macrophages were isolated from lung resections (<i>n</i> = 68) and treated with hemin or ferric ammonium citrate (50, 100 or 200 μM). Lung macrophage phenotype marker gene expression was measured by qPCR. The phagocytosis of Non-typeable <i>Haemophilus influenzae</i> (NTHi) was measured by flow cytometry. Cytokine production in response to NTHi in iron-treated macrophages was measured by ELISA. Lung macrophage iron levels were significantly correlated with RBC coverage of the alveolar space (<i>r</i> = 0.31, <i>p</i> = 0.02). Furthermore, RBC coverage and lung macrophage iron were significantly increased in COPD patients and correlated with airflow obstruction. Hemin treatment downregulated CD36, CD163, HLA-DR, CD38, TLR4, CD14 and MARCO gene expression. Hemin-treated macrophages also impaired production of pro-inflammatory cytokines in response to NTHi exposure, and decreased phagocytosis of NTHi (200 μM: 35% decrease; <i>p</i> = 0.03). RBCs are a plausible source of pulmonary iron overload in COPD. RBC-derived iron dysregulates macrophage phenotype and function. |
| first_indexed | 2024-03-10T04:33:52Z |
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| language | English |
| last_indexed | 2024-03-10T04:33:52Z |
| publishDate | 2021-12-01 |
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| series | Biomedicines |
| spelling | doaj.art-9a715e801c01449398825a4069b3d0022023-11-23T03:57:55ZengMDPI AGBiomedicines2227-90592021-12-01912193910.3390/biomedicines9121939Red Blood Cell-Derived Iron Alters Macrophage Function in COPDJames M. Baker0Molly Hammond1Josiah Dungwa2Rajesh Shah3Angeles Montero-Fernandez4Andrew Higham5Simon Lea6Dave Singh7Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and Manchester University NHS Foundation Trust, Manchester M13 9PL, UKMedicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester M23 9QZ, UKMedicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester M23 9QZ, UKDepartment of Thoracic Surgery, Manchester University Hospital NHS Foundation Trust, Manchester M13 9WL, UKDepartment of Histopathology, Manchester University Hospital NHS Foundation Trust, Manchester M13 9WL, UKDivision of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and Manchester University NHS Foundation Trust, Manchester M13 9PL, UKDivision of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and Manchester University NHS Foundation Trust, Manchester M13 9PL, UKDivision of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester and Manchester University NHS Foundation Trust, Manchester M13 9PL, UKLung macrophage iron levels are increased in COPD patients. Lung macrophage iron levels are thought to be increased by cigarette smoke, but the role of red blood cells (RBCs) as a source of iron has not been investigated. We investigate RBCs as a potential source of alveolar iron in COPD, and determine the effect of RBC-derived iron on macrophage function. We used lung tissue sections to assess RBC coverage of the alveolar space, iron and ferritin levels in 11 non-smokers (NS), 15 smokers (S) and 32 COPD patients. Lung macrophages were isolated from lung resections (<i>n</i> = 68) and treated with hemin or ferric ammonium citrate (50, 100 or 200 μM). Lung macrophage phenotype marker gene expression was measured by qPCR. The phagocytosis of Non-typeable <i>Haemophilus influenzae</i> (NTHi) was measured by flow cytometry. Cytokine production in response to NTHi in iron-treated macrophages was measured by ELISA. Lung macrophage iron levels were significantly correlated with RBC coverage of the alveolar space (<i>r</i> = 0.31, <i>p</i> = 0.02). Furthermore, RBC coverage and lung macrophage iron were significantly increased in COPD patients and correlated with airflow obstruction. Hemin treatment downregulated CD36, CD163, HLA-DR, CD38, TLR4, CD14 and MARCO gene expression. Hemin-treated macrophages also impaired production of pro-inflammatory cytokines in response to NTHi exposure, and decreased phagocytosis of NTHi (200 μM: 35% decrease; <i>p</i> = 0.03). RBCs are a plausible source of pulmonary iron overload in COPD. RBC-derived iron dysregulates macrophage phenotype and function.https://www.mdpi.com/2227-9059/9/12/1939lung macrophageironchronic obstructive pulmonary diseasephagocytosis |
| spellingShingle | James M. Baker Molly Hammond Josiah Dungwa Rajesh Shah Angeles Montero-Fernandez Andrew Higham Simon Lea Dave Singh Red Blood Cell-Derived Iron Alters Macrophage Function in COPD Biomedicines lung macrophage iron chronic obstructive pulmonary disease phagocytosis |
| title | Red Blood Cell-Derived Iron Alters Macrophage Function in COPD |
| title_full | Red Blood Cell-Derived Iron Alters Macrophage Function in COPD |
| title_fullStr | Red Blood Cell-Derived Iron Alters Macrophage Function in COPD |
| title_full_unstemmed | Red Blood Cell-Derived Iron Alters Macrophage Function in COPD |
| title_short | Red Blood Cell-Derived Iron Alters Macrophage Function in COPD |
| title_sort | red blood cell derived iron alters macrophage function in copd |
| topic | lung macrophage iron chronic obstructive pulmonary disease phagocytosis |
| url | https://www.mdpi.com/2227-9059/9/12/1939 |
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