Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study

<p>Abstract</p> <p>Background</p> <p>Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulm...

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Main Authors: Roggli Victor L, Crissman Kay M, Richards Judy H, Stonehuerner Jacqueline G, Ghio Andrew J, Piantadosi Claude A, Carraway Martha
Format: Article
Language:English
Published: BMC 2008-01-01
Series:Respiratory Research
Online Access:http://respiratory-research.com/content/9/1/10
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spelling doaj-2e402116ba5a4d39b065f5eae82eaaed2020-11-25T00:23:16ZengBMCRespiratory Research1465-99212008-01-01911010.1186/1465-9921-9-10Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control studyRoggli Victor LCrissman Kay MRichards Judy HStonehuerner Jacqueline GGhio Andrew JPiantadosi Claude ACarraway Martha<p>Abstract</p> <p>Background</p> <p>Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosis (PAP), we tested the hypothesis that idiopathic PAP is associated with an altered iron homeostasis in the human lung.</p> <p>Methods</p> <p>Healthy volunteers (n = 20) and patients with idiopathic PAP (n = 20) underwent bronchoalveolar lavage and measurements were made of total protein, iron, tranferrin, transferrin receptor, lactoferrin, and ferritin. Histochemical staining for iron and ferritin was done in the cell pellets from control subjects and PAP patients, and in lung specimens of patients without cardiopulmonary disease and with PAP. Lavage concentrations of urate, glutathione, and ascorbate were also measured as indices of oxidative stress.</p> <p>Results</p> <p>Lavage concentrations of iron, transferrin, transferrin receptor, lactoferrin, and ferritin were significantly elevated in PAP patients relative to healthy volunteers. The cells of PAP patients had accumulated significant iron and ferritin, as well as considerable amounts of extracellular ferritin. Immunohistochemistry for ferritin in lung tissue revealed comparable amounts of this metal-storage protein in the lower respiratory tract of PAP patients both intracellularly and extracellularly. Lavage concentrations of ascorbate, glutathione, and urate were significantly lower in the lavage fluid of the PAP patients.</p> <p>Conclusion</p> <p>Iron homeostasis is altered in the lungs of patients with idiopathic PAP, as large amounts of catalytically-active iron and low molecular weight anti-oxidant depletion are present. These findings suggest a metal-catalyzed oxidative stress in the maintenance of this disease.</p> http://respiratory-research.com/content/9/1/10
collection DOAJ
language English
format Article
sources DOAJ
author Roggli Victor L
Crissman Kay M
Richards Judy H
Stonehuerner Jacqueline G
Ghio Andrew J
Piantadosi Claude A
Carraway Martha
spellingShingle Roggli Victor L
Crissman Kay M
Richards Judy H
Stonehuerner Jacqueline G
Ghio Andrew J
Piantadosi Claude A
Carraway Martha
Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
Respiratory Research
author_facet Roggli Victor L
Crissman Kay M
Richards Judy H
Stonehuerner Jacqueline G
Ghio Andrew J
Piantadosi Claude A
Carraway Martha
author_sort Roggli Victor L
title Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
title_short Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
title_full Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
title_fullStr Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
title_full_unstemmed Iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
title_sort iron homeostasis and oxidative stress in idiopathic pulmonary alveolar proteinosis: a case-control study
publisher BMC
series Respiratory Research
issn 1465-9921
publishDate 2008-01-01
description <p>Abstract</p> <p>Background</p> <p>Lung injury caused by both inhaled dusts and infectious agents depends on increased availability of iron and metal-catalyzed oxidative stress. Because inhaled particles, such as silica, and certain infections can cause secondary pulmonary alveolar proteinosis (PAP), we tested the hypothesis that idiopathic PAP is associated with an altered iron homeostasis in the human lung.</p> <p>Methods</p> <p>Healthy volunteers (n = 20) and patients with idiopathic PAP (n = 20) underwent bronchoalveolar lavage and measurements were made of total protein, iron, tranferrin, transferrin receptor, lactoferrin, and ferritin. Histochemical staining for iron and ferritin was done in the cell pellets from control subjects and PAP patients, and in lung specimens of patients without cardiopulmonary disease and with PAP. Lavage concentrations of urate, glutathione, and ascorbate were also measured as indices of oxidative stress.</p> <p>Results</p> <p>Lavage concentrations of iron, transferrin, transferrin receptor, lactoferrin, and ferritin were significantly elevated in PAP patients relative to healthy volunteers. The cells of PAP patients had accumulated significant iron and ferritin, as well as considerable amounts of extracellular ferritin. Immunohistochemistry for ferritin in lung tissue revealed comparable amounts of this metal-storage protein in the lower respiratory tract of PAP patients both intracellularly and extracellularly. Lavage concentrations of ascorbate, glutathione, and urate were significantly lower in the lavage fluid of the PAP patients.</p> <p>Conclusion</p> <p>Iron homeostasis is altered in the lungs of patients with idiopathic PAP, as large amounts of catalytically-active iron and low molecular weight anti-oxidant depletion are present. These findings suggest a metal-catalyzed oxidative stress in the maintenance of this disease.</p>
url http://respiratory-research.com/content/9/1/10
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