Elevated iron levels in airspace macrophages (AMs) are linked to chronic obstructive pulmonary disease (COPD) exacerbation and may drive the disease’s pathophysiology. Cigarette smoke exposure leads to iron dysregulation in AMs, impacting immune function and increasing infection risk. Murine models of cigarette smoke exposure replicate this AM iron loading, showing dysregulated iron metabolic proteins and immune function. Depleting NCOA4, a key regulator of iron metabolism, reduces iron accumulation but may impair bacterial clearance during infections. These findings suggest that while iron overload in AMs has negative effects, disrupting iron homeostasis can hinder macrophage function, particularly during infection-triggered exacerbations.
Translational studies are exploring iron chelation therapies in humans, including a proof-of-concept study with deferiprone, an iron chelator. The study showed that deferiprone could reduce iron levels in AMs from smokers but not from patients with COPD, with ongoing research investigating biological differences or treatment efficacy. Additional studies focus on the transcriptomic analysis of AMs from smokers and patients with COPD, with findings aligning with murine models. These insights are expected to lead to further investigations into the potential of iron regulation as a therapeutic strategy in COPD, with manuscripts prepared for submission to the American Thoracic Society.
Reference: Zhang W. Abnormal Iron Homeostasis in Alveolar Macrophages: Implications for COPD Pathogenesis. HCPLive. Published April 18, 2025. Accessed May 2, 2025. https://www.hcplive.com/view/abnormal-iron-homeostasis-alveolar-macrophages-implications-copd-pathogenesis
