Increased iron sequestration in alveolar macrophages in chronic obstructive pulmonary disease.

Abstract

Free iron in lung can cause the generation of reactive oxygen species, an important factor in chronic obstructive pulmonary disease (COPD) pathogenesis. Iron accumulation has been implicated in oxidative stress in other diseases, such as Alzheimer's and Parkinson's diseases, but little is known about iron accumulation in COPD. We sought to determine if iron content and the expression of iron transport and/or storage genes in lung differ between controls and COPD subjects, and whether changes in these correlate with airway obstruction. Explanted lung tissue was obtained from transplant donors, GOLD 2-3 COPD subjects, and GOLD 4 lung transplant recipients, and bronchoalveolar lavage (BAL) cells were obtained from non-smokers, healthy smokers, and GOLD 1-3 COPD subjects. Iron-positive cells were quantified histologically, and the expression of iron uptake (transferrin and transferrin receptor), storage (ferritin) and export (ferroportin) genes was examined by real-time RT-PCR assay. Percentage of iron-positive cells and expression levels of iron metabolism genes were examined for correlations with airflow limitation indices (forced expiratory volume in the first second (FEV1) and the ratio between FEV1 and forced vital capacity (FEV1/FVC)). The alveolar macrophage was identified as the predominant iron-positive cell type in lung tissues. Furthermore, the quantity of iron deposit and the percentage of iron positive macrophages were increased with COPD and emphysema severity. The mRNA expression of iron uptake and storage genes transferrin and ferritin were significantly increased in GOLD 4 COPD lungs compared to donors (6.9 and 3.22 fold increase, respectively). In BAL cells, the mRNA expression of transferrin, transferrin receptor and ferritin correlated with airway obstruction. These results support activation of an iron sequestration mechanism by alveolar macrophages in COPD, which we postulate is a protective mechanism against iron induced oxidative stress.

• Authors: Quentin Philippot, Gaëtan Deslée, Tracy L Adair-Kirk, Jason C Woods, Derek Byers, Susan Conradi, Sandra Dury, Jeanne Marie Perotin, François Lebargy, Christelle Cassan, Richard Le Naour, Michael J Holtzman, Richard A Pierce
• Journal: PloS one (PLoS One) Vol. 9 Issue 5 Pg. e96285 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24789352 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Receptors, Transferrin
• Transferrin
• Iron

Topics

• Adult
• Female
• Gene Expression Regulation
• Humans
• Iron (metabolism)
• Macrophages, Alveolar (metabolism, pathology)
• Male
• Middle Aged
• Pulmonary Disease, Chronic Obstructive (metabolism, pathology)
• Receptors, Transferrin (genetics)
• Transferrin (genetics)
• Young Adult