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Red Blood Cell-Derived Iron Alters Macrophage Function in COPD.
Baker, James M; Hammond, Molly; Dungwa, Josiah; Shah, Rajesh; Montero-Fernandez, Angeles; Higham, Andrew; Lea, Simon; Singh, Dave.
  • Baker JM; Division 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, UK.
  • Hammond M; Medicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester M23 9QZ, UK.
  • Dungwa J; Medicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester M23 9QZ, UK.
  • Shah R; Department of Thoracic Surgery, Manchester University Hospital NHS Foundation Trust, Manchester M13 9WL, UK.
  • Montero-Fernandez A; Department of Histopathology, Manchester University Hospital NHS Foundation Trust, Manchester M13 9WL, UK.
  • Higham A; Division 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, UK.
  • Lea S; Division 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, UK.
  • Singh D; Division 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, UK.
Biomedicines ; 9(12)2021 Dec 17.
Article in English | MEDLINE | ID: covidwho-1591484
ABSTRACT
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 (n = 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 Haemophilus influenzae (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 (r = 0.31, p = 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; p = 0.03). RBCs are a plausible source of pulmonary iron overload in COPD. RBC-derived iron dysregulates macrophage phenotype and function.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article Affiliation country: Biomedicines9121939

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2021 Document Type: Article Affiliation country: Biomedicines9121939