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. 2017 Nov 1;196(9):1103-1112.
doi: 10.1164/rccm.201702-0311PP.

The "Iron"-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

Suzanne M Cloonan  1 , Sharon Mumby  2 , Ian M Adcock  2 , Augustine M K Choi  1   3 , Kian Fan Chung  2 , Gregory J Quinlan  4
Affiliations

The "Iron"-y of Iron Overload and Iron Deficiency in Chronic Obstructive Pulmonary Disease

Suzanne M Cloonan et al. Am J Respir Crit Care Med. .
No abstract available

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Figures

Figure 1.
Figure 1.
Iron import and export in the lung. Both alveolar macrophages and the bronchial and alveolar epithelial cells are able to sequester iron through transferrin receptor 1, divalent metal transporter 1 (DMT1, also known as SLC11A2), and in macrophages and neutrophils by natural resistance-associated macrophage protein 1 (NRAMP1, also known as SLC11A1). Lung cells also express other iron-uptake molecules, including ZIP-14 (also known as SLC39A14) and the lactoferrin receptor low-density lipoprotein receptor–related protein 1 (LRP1). Lung epithelial cells, alveolar macrophages, and endothelial cells transport iron out of the cell via the transmembrane iron transporter ferroportin (also known as SLC40A1). AECI = alveolar epithelial cell type I; AECII = alveolar epithelial cell type II; AM = alveolar macrophage; BM = basement membrane; EC = endothelial cell; RBC = red blood cell; TfR1 = transferrin receptor 1; ZIP14 = zinc transporter ZIP14.
Figure 2.
Figure 2.
Hepcidin and systemic iron homeostasis in chronic obstructive pulmonary disease (COPD). Hepcidin (encoded by HAMP) is a hormone produced chiefly in the liver, which regulates, and is in turn regulated by, systemic iron levels. Hepcidin expression and release is induced by increased serum iron; by bone morphogenetic protein 6 (BMP6) signaling; and by a number of proinflammatory cytokines, including IL-6 and IL-22. Up-regulation of hepcidin expression results in ferroportin endocytosis and proteolysis, preventing cellular iron export and reducing the influx of iron into the plasma from stores, as well as blocking further absorption of dietary iron. This may have profound consequences for the cell, particularly if iron-uptake stratagems remain operational, and may result in cellular iron accumulation and systemic hypoferremia or iron-deficiency anemia. Consistent with increased iron loading into cells, tissues, and iron-chelating proteins, serum hepcidin is increased in patients with COPD. Increased hepcidin may result in less iron delivery to extracellular fluid, in macrophages failing to release recycled iron, and in a rapid drop in systemic iron levels, leading to iron deficiency. AECII = alveolar epithelial cell type II; AM = alveolar macrophage; NTBI = non-transferrin bound iron.
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