Smoking-induced iron dysregulation in the lung
Open accessAbstract
Iron is one of the most abundant transition elements and is indispensable for almost all organisms. While the ability of iron to participate in redox chemistry is an essential requirement for participation in a range of vital enzymatic reactions, this same feature of iron also makes it dangerous in the generation of hydroxyl radicals and superoxide anions. Given the high local oxygen tensions in the lung, the regulation of iron acquisition, utilization, and storage therefore becomes vitally important, perhaps more so than in any other biological system. Iron plays a critical role in the biology of essentially every cell type in the lung, and in particular, changes in iron levels have important ramifications on immune function and the local lung microenvironment. There is substantial evidence that cigarette smoke causes iron dysregulation, with the implication that iron may be the link between smoking and smoking-related lung diseases. A better understanding of the connection between cigarette smoke, iron, and respiratory diseases will help to elucidate pathogenic mechanisms and aid in the identification of novel therapeutic targets.
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Cigarette smoke is known to complex Fe which is deposited in ferritin as ferrihydrite.
“CS is known to complex Fe which is deposited in ferritin as ferrihydrite [12, 34–36].”
From An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma (2023) · cites this paper as [12]
The Introduction says cigarette-smoke particles are thought to complex host iron. The lung-epithelium section reports increased iron and ferritin after smoke exposure, but our copy does not say that smoke-complexed iron is deposited in ferritin as ferrihydrite. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe AM also scavenge Fe from senescent red blood cells, storing the Fe in ferritin within the AM for Fe recycling.
“The AM also scavenge Fe from senescent red blood cells, storing the Fe in ferritin (an Fe transport protein), within the AM for Fe recycling [12].”
From An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma (2023) · cites this paper as [12]
The ‘Iron Handling in the Lung’ section says alveolar macrophages sequester iron and store it in ferritin. ‘Introduction to Iron Metabolism’ says iron is recycled from senescent erythrocytes, but does not identify alveolar macrophages as the cells that scavenge those erythrocytes. It also calls ferritin an iron-storage protein, not an iron-transport protein. The supplied passages give no page numbers. (LLM, conf=0.85)
Experimental — accuracy not yet measuredIn smoking patients, Fe complexation by CS leads to more pronounced Fe mobilisation and thus a continuous supply of Fe to the AFBs.
“in smoking patients Fe complexation by CS leads to a more pronounced Fe mobilisation [12, 34–36, 39] and thus a continuous supply of Fe to the AFBs.”
From An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma (2023) · cites this paper as [12]
The Introduction (page unavailable) says cigarette-smoke particles are thought to complex host iron and reports higher lung iron levels in smokers. It does not establish that complexation causes greater iron mobilisation; the proposed continuous supply to AFBs is an inference following the citation, not a finding this source reports. (LLM, conf=0.82)
Experimental — accuracy not yet measuredThe denser layers and higher Fe concentration in smoking patients are likely due to CS complexation of Fe.
“likely due to the CS complexation of Fe, as mentioned previously [12, 34–36]”
From An investigation of the internal morphology of asbestos ferruginous bodies: constraining their role in the onset of malignant mesothelioma (2023) · cites this paper as [12]
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Deficiency in the divalent metal transporter 1 increases bleomycin-induced lung injury
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Flagged first, then by citations
Research works printed but not linked: 1
- [171]Ghio AJ, Hilborn ED, Stonehuerner JG, Dailey LA, Carter JD, Richards JH, Crissman KM, Foronjy RF, Uyeminami DL, Pinkerton KE, Particulate matter in cigarette smoke alters iron homeostasis to produce a biological effect, American Journal of Respiratory and Critical Care Medicine 178(11) (2008) 1130– 1138. 18723436
Cited by
Sorted by citations
Avramescu, M.-L., Potiszil, C., Kunihiro, T., Okabe, K., & Nakamura, E. (2023) · Particle and Fibre Toxicology · doi:10.1186/s12989-023-00522-0 · Cited by 12 · see citing works
“The AM also scavenge Fe from senescent red blood cells, storing the Fe in ferritin (an Fe transport protein), within the AM for Fe recycling [12].”
Background
- Authors
- Zhang, W. Z., Butler, J. J., & Cloonan, S. M.
- Affiliations
- NewYork–Presbyterian Hospital (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Cloonan, Suzanne M.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 133
- Pages
- 238-247
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC6355389
- OpenAlex
- W2885244866
- Cited by
- 62
- References
- 179
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 3 · 2023: 14 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 6
- FWCI
- 0.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- US National Institute of Health–National Heart, Lung and Blood Institute (R00-HL125899)
- CHEST Foundation Research Grant in Chronic Obstructive Pulmonary Disease
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Ferroptosis and cancer prognosis
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Keywords
- iron dysregulation, cigarette smoke, iron acquisition, iron storage, oxidative stress, hydroxyl radicals, superoxide, smoking-related lung disease, lung microenvironment, lung immunity
- MeSH terms
- Tobacco Smoking, Humans, Iron, Lung, Lung Diseases, Oxidation-Reduction, Superoxides, Hydroxyl Radical
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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