Red Blood Cell-Derived Iron Alters Macrophage Function in COPD

Area of Science:

• Pulmonary Medicine
• Immunology
• Hematology

Background:

• Lung macrophage iron is elevated in Chronic Obstructive Pulmonary Disease (COPD).
• Cigarette smoke is a suspected cause, but the role of red blood cells (RBCs) as an iron source is unexplored.

Purpose of the Study:

• Investigate RBCs as a source of alveolar iron in COPD.
• Determine how RBC-derived iron impacts macrophage function.

Main Methods:

• Assessed RBC coverage, iron, and ferritin in lung tissue from non-smokers, smokers, and COPD patients.
• Isolated lung macrophages and treated them with hemin or ferric ammonium citrate.
• Measured macrophage phenotype gene expression, phagocytosis of *Haemophilus influenzae* (NTHi), and cytokine production.

Main Results:

• Lung macrophage iron correlated with RBC alveolar coverage (r=0.31, p=0.02).
• COPD patients showed increased RBC coverage and macrophage iron, linked to airflow obstruction.
• Hemin treatment altered macrophage gene expression, reduced NTHi phagocytosis (35% decrease at 200 μM, p=0.03), and impaired cytokine production.

Conclusions:

• RBCs are a likely source of pulmonary iron overload in COPD.
• RBC-derived iron dysregulates macrophage phenotype and function, contributing to COPD pathogenesis.