| Autor: |
James M. Baker, Molly Hammond, Josiah Dungwa, Rajesh Shah, Angeles Montero-Fernandez, Andrew Higham, Simon Lea, Dave Singh |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Biomedicines, Vol 9, Iss 12, p 1939 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2227-9059 |
| DOI: |
10.3390/biomedicines9121939 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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