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The role of iron in pulmonary pathology.

Khiroya H, Turner AM - Multidiscip Respir Med (2015)

Bottom Line: The effects of cigarette smoke are detailed in this article, particularly in relation to lung conditions that favour the upper lobes, such as emphysema and lung cancer.Clinical applications of iron homeostasis are also discussed in this review, especially looking at the pathophysiology of chronic obstructive pulmonary disease, lung cancer, pulmonary infections and acute respiratory distress syndrome.Promising new treatments involving iron are also covered.

View Article: PubMed Central - PubMed

Affiliation: School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, B15 2TT UK ; Centre for Translational Inflammation Research, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2GW UK.

ABSTRACT
Respiratory disease accounts for a large proportion of emergency admissions to hospital and diseaseassociated mortality. Genetic association studies demonstrate a link between iron metabolism and pulmonary disease phenotypes. IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which has a key role in iron homeostasis. This review addresses pathways involved in iron metabolism, particularly focusing on the role of IREB2. In addition to this, environmental factors also influence phenotypic variation in respiratory disease, for example inhaled iron from cigarette smoke is deposited in the lung and causes tissue damage by altering iron homeostasis. The effects of cigarette smoke are detailed in this article, particularly in relation to lung conditions that favour the upper lobes, such as emphysema and lung cancer. Clinical applications of iron homeostasis are also discussed in this review, especially looking at the pathophysiology of chronic obstructive pulmonary disease, lung cancer, pulmonary infections and acute respiratory distress syndrome. Promising new treatments involving iron are also covered.

No MeSH data available.


Related in: MedlinePlus

Iron homeostasis: the transferrin-to-cell cycle. At neutral pH, apotranferrin is released at the cell membrane. The iron-transferrin complex then binds to its receptor at the cell membrane and endosomal fusion occurs. A complex is then formed with divalent metal transporter 1. At pH 5.5 iron is reduced and released to be used by the mitcochodria or stored as ferritin. The Golgi body package the apotransferrin-receptor complex into a vesicle and it is transported back to the cell membrane
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Fig1: Iron homeostasis: the transferrin-to-cell cycle. At neutral pH, apotranferrin is released at the cell membrane. The iron-transferrin complex then binds to its receptor at the cell membrane and endosomal fusion occurs. A complex is then formed with divalent metal transporter 1. At pH 5.5 iron is reduced and released to be used by the mitcochodria or stored as ferritin. The Golgi body package the apotransferrin-receptor complex into a vesicle and it is transported back to the cell membrane

Mentions: There is a separate second system that regulates iron homeostasis within cells. In the bloodstream, iron binds to transferrin [11]. Transferrin receptor 1 is expressed on the cell membrane, and most cells can regulate the influx of iron via this channel [12]. Figure 1 demonstrates the transferrin-to-cell cycle in more detail. Non-tranferrin bound iron species are found in the plasma, the main form is thought to be Fe3+ bound to citrate [13]. Mechanisms surrounding cellular uptake are unknown but thought to be independent of endocytosis [13]. Iron regulatory proteins 1 and 2 (IRP1 and IRP2) register iron concentrations in the cytosol [14] and post-transcriptionally regulate expression of transferrin receptors and iron metabolism genes to optimise cellular iron availability [15]. Macrophages provide an additional route for iron concentrations to be maintained intracellularly via phagoytosis of damaged erythrocytes [10]. The phagocytosed iron is either stored as ferritin in the cytoplasm and is subject to regulation by the IRPs, or travels through ferroportin to the extracellular fluid [10].Fig. 1


The role of iron in pulmonary pathology.

Khiroya H, Turner AM - Multidiscip Respir Med (2015)

Iron homeostasis: the transferrin-to-cell cycle. At neutral pH, apotranferrin is released at the cell membrane. The iron-transferrin complex then binds to its receptor at the cell membrane and endosomal fusion occurs. A complex is then formed with divalent metal transporter 1. At pH 5.5 iron is reduced and released to be used by the mitcochodria or stored as ferritin. The Golgi body package the apotransferrin-receptor complex into a vesicle and it is transported back to the cell membrane
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4666040&req=5

Fig1: Iron homeostasis: the transferrin-to-cell cycle. At neutral pH, apotranferrin is released at the cell membrane. The iron-transferrin complex then binds to its receptor at the cell membrane and endosomal fusion occurs. A complex is then formed with divalent metal transporter 1. At pH 5.5 iron is reduced and released to be used by the mitcochodria or stored as ferritin. The Golgi body package the apotransferrin-receptor complex into a vesicle and it is transported back to the cell membrane
Mentions: There is a separate second system that regulates iron homeostasis within cells. In the bloodstream, iron binds to transferrin [11]. Transferrin receptor 1 is expressed on the cell membrane, and most cells can regulate the influx of iron via this channel [12]. Figure 1 demonstrates the transferrin-to-cell cycle in more detail. Non-tranferrin bound iron species are found in the plasma, the main form is thought to be Fe3+ bound to citrate [13]. Mechanisms surrounding cellular uptake are unknown but thought to be independent of endocytosis [13]. Iron regulatory proteins 1 and 2 (IRP1 and IRP2) register iron concentrations in the cytosol [14] and post-transcriptionally regulate expression of transferrin receptors and iron metabolism genes to optimise cellular iron availability [15]. Macrophages provide an additional route for iron concentrations to be maintained intracellularly via phagoytosis of damaged erythrocytes [10]. The phagocytosed iron is either stored as ferritin in the cytoplasm and is subject to regulation by the IRPs, or travels through ferroportin to the extracellular fluid [10].Fig. 1

Bottom Line: The effects of cigarette smoke are detailed in this article, particularly in relation to lung conditions that favour the upper lobes, such as emphysema and lung cancer.Clinical applications of iron homeostasis are also discussed in this review, especially looking at the pathophysiology of chronic obstructive pulmonary disease, lung cancer, pulmonary infections and acute respiratory distress syndrome.Promising new treatments involving iron are also covered.

View Article: PubMed Central - PubMed

Affiliation: School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, B15 2TT UK ; Centre for Translational Inflammation Research, Queen Elizabeth Hospital, Mindelsohn Way, Edgbaston, Birmingham, B15 2GW UK.

ABSTRACT
Respiratory disease accounts for a large proportion of emergency admissions to hospital and diseaseassociated mortality. Genetic association studies demonstrate a link between iron metabolism and pulmonary disease phenotypes. IREB2 is a gene that produces iron regulatory protein 2 (IRP2), which has a key role in iron homeostasis. This review addresses pathways involved in iron metabolism, particularly focusing on the role of IREB2. In addition to this, environmental factors also influence phenotypic variation in respiratory disease, for example inhaled iron from cigarette smoke is deposited in the lung and causes tissue damage by altering iron homeostasis. The effects of cigarette smoke are detailed in this article, particularly in relation to lung conditions that favour the upper lobes, such as emphysema and lung cancer. Clinical applications of iron homeostasis are also discussed in this review, especially looking at the pathophysiology of chronic obstructive pulmonary disease, lung cancer, pulmonary infections and acute respiratory distress syndrome. Promising new treatments involving iron are also covered.

No MeSH data available.


Related in: MedlinePlus