Disruption of iron homeostasis and lung disease.
As a result of a direct exchange with the external environment, the lungs are exposed to both iron and agents with a capacity to disrupt the homeostasis of this metal (e.g. particles). An increased availability of catalytically reactive iron can result from these exposures and, by generating an oxidative stress, this metal can contribute to tissue injury. By importing this Fe(3+) into cells for storage in a chemically less reactive form, the lower respiratory tract demonstrates an ability to mitigate both the oxidative stress presented by iron and its potential for tissue injury. This means that detoxification is accomplished by chemical reduction to Fe(2+) (e.g. by duodenal cytochrome b and other ferrireductases), iron import (e.g. by divalent metal transporter 1 and other transporters), and storage in ferritin. The metal can subsequently be exported from the cell (e.g. by ferroportin 1) in a less reactive state relative to that initially imported. Iron is then transported out of the lung via the mucociliary pathway or blood and lymphatic pathways to the reticuloendothelial system for long term storage. This coordinated handling of iron in the lung appears to be disrupted in several acute diseases on the lung including infections, acute respiratory distress syndrome, transfusion-related acute lung injury, and ischemia-reperfusion. Exposures to bleomycin, dusts and fibers, and paraquat similarly alter iron homeostasis in the lung to affect an oxidative stress. Finally, iron homeostasis is disrupted in numerous chronic lung diseases including pulmonary alveolar proteinosis, transplantation, cigarette smoking, and cystic fibrosis.
Ghio
Andrew J
AJ
Human Studies Division, ORD, NHEERL, US EPA, Campus Box 7315, 104 Mason Farm Road, Chapel Hill, NC 27599-7315, USA. ghio.andy@epa.gov
D055371:Acute Lung Injury / Q000503:physiopathology; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics; D020895:Enterocytes / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008171:Lung Diseases / Q000378:metabolism*; D055370:Lung Injury / Q000503:physiopathology; D018384:Oxidative Stress; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D005293:Ferritins; D007501:Iron; D000099236:Solute Carrier Family 11, Member 2