Iron Metabolism and Lung Health

The lung requires a finely tuned balance of iron to support essential processes such as oxygen transport, cellular respiration and innate immunity while avoiding iron-catalysed oxidative injury. Systemic and local regulators coordinate iron uptake, storage and export in airway epithelial cells and alveolar macrophages. The central hormone in systemic control, hepcidin, limits iron egress by binding to the iron exporter ferroportin, whereas ferritin stores excess intracellular iron in a non-reactive form. In the pulmonary environment, specialised mechanisms of iron handling intersect with oxygen sensing and host defence. Dysregulated iron homeostasis contributes to the pathogenesis and progression of chronic obstructive pulmonary disease, asthma, pulmonary infections and acute respiratory distress by promoting reactive oxygen species formation, impairing macrophage function and fostering microbial growth. Emerging evidence highlights the dual role of iron as both a nutrient for invading pathogens and a mediator of host immune responses. Advances in imaging and molecular profiling have begun to reveal the spatial distribution of iron in lung tissue, the cell-specific expression of iron-regulatory proteins and the impact of inflammatory cytokines on local iron balance. A deeper understanding of these pathways is driving the development of therapeutics aimed at modulating iron availability to attenuate oxidative damage and improve infection control, with potential applications across a spectrum of respiratory diseases.

Research from Nature Portfolio

Recent imaging studies using high-resolution mass spectrometry have mapped iron distribution in lung tissue from severe chronic obstructive pulmonary disease patients. These investigations uncovered markedly elevated and heterogeneously localised iron deposits within alveolar macrophages and epithelial cells, suggesting compartmentalised iron overload as a contributor to oxidative stress and tissue damage. Multivariate analyses linked iron accumulation patterns to lipid alterations, pointing to combined dysregulation of metal and lipid metabolism as a feature of advanced lung pathology.

Iron Metabolism and Lung Health publication trend

The graph below shows the total number of articles in iron metabolism and lung health across all publications each year (not limited to Nature Index journals).

Technical terms

Hepcidin: A peptide hormone produced by the liver and lung that binds ferroportin to regulate systemic and local iron export.

Ferroportin: The sole known cellular iron exporter, whose surface expression is controlled by hepcidin binding.

Ferritin: A multi-subunit protein that stores iron in a soluble, non-toxic form within cells.

Alveolar macrophage: A resident immune cell in the lung alveoli that sequesters iron and mediates clearance of pathogens and debris.

Oxidative stress: Cellular damage caused by an overproduction of reactive oxygen species, often enhanced by free iron catalysis.

Nutritional immunity: The host strategy of restricting pathogen access to essential metals such as iron during infection.

References

1. Iron Homeostasis in the Lungs—A Balance between Health and Disease. Pharmaceuticals (2019).
2. Iron in Lung Pathology. Pharmaceuticals (2019).
3. Nutritional immunity: the impact of metals on lung immune cells and the airway microbiome during chronic respiratory disease. Respiratory Research (2021).
4. Increased Iron Sequestration in Alveolar Macrophages in Chronic Obtructive Pulmonary Disease. PLOS ONE (2014).
5. ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients. Scientific Reports (2019).
6. Iron in airway macrophages and infective exacerbations of chronic obstructive pulmonary disease. Respiratory Research (2022).