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Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD
We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD. We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047017/ https://www.ncbi.nlm.nih.gov/pubmed/24901869 http://dx.doi.org/10.1371/journal.pone.0098571 |
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author | Tran, Hai B. Ahern, Jessica Hodge, Greg Holt, Phillip Dean, Melinda M. Reynolds, Paul N. Hodge, Sandra |
author_facet | Tran, Hai B. Ahern, Jessica Hodge, Greg Holt, Phillip Dean, Melinda M. Reynolds, Paul N. Hodge, Sandra |
author_sort | Tran, Hai B. |
collection | PubMed |
description | We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD. We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function) were reduced in the airways but not circulation of COPD patients. We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances. We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages. Oligomeric structure of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2′-azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue native PAGE. Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi) and expression of macrophage scavenger receptors. Oxidation disrupted higher order MBL oligomers. This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively). Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels. Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1) in the presence of pdMBL that was abrogated in the presence of oxMBL. We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease. |
format | Online Article Text |
id | pubmed-4047017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-40470172014-06-09 Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD Tran, Hai B. Ahern, Jessica Hodge, Greg Holt, Phillip Dean, Melinda M. Reynolds, Paul N. Hodge, Sandra PLoS One Research Article We have previously established that a defect in the ability of alveolar macrophages (AM) to phagocytose apoptotic cells (efferocytosis) and pathogens is a potential therapeutic target in COPD. We further showed that levels of mannose binding lectin (MBL; required for effective macrophage phagocytic function) were reduced in the airways but not circulation of COPD patients. We hypothesized that increased oxidative stress in the airway could be a cause for such disturbances. We therefore studied the effects of oxidation on the structure of the MBL molecule and its functional interactions with macrophages. Oligomeric structure of plasma derived MBL (pdMBL) before and after oxidation (oxMBL) with 2,2′-azobis(2-methylpropionamidine)dihydrochroride (AAPH) was investigated by blue native PAGE. Macrophage function in the presence of pd/oxMBL was assessed by measuring efferocytosis, phagocytosis of non-typeable Haemophilus influenzae (NTHi) and expression of macrophage scavenger receptors. Oxidation disrupted higher order MBL oligomers. This was associated with changed macrophage function evident by a significantly reduced capacity to phagocytose apoptotic cells and NTHi in the presence of oxMBL vs pdMBL (eg, NTHi by 55.9 and 27.0% respectively). Interestingly, oxidation of MBL significantly reduced macrophage phagocytic ability to below control levels. Flow cytometry and immunofluorescence revealed a significant increase in expression of macrophage scavenger receptor (SRA1) in the presence of pdMBL that was abrogated in the presence of oxMBL. We show the pulmonary macrophage dysfunction in COPD may at least partially result from an oxidative stress-induced effect on MBL, and identify a further potential therapeutic strategy for this debilitating disease. Public Library of Science 2014-06-05 /pmc/articles/PMC4047017/ /pubmed/24901869 http://dx.doi.org/10.1371/journal.pone.0098571 Text en © 2014 Tran et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Tran, Hai B. Ahern, Jessica Hodge, Greg Holt, Phillip Dean, Melinda M. Reynolds, Paul N. Hodge, Sandra Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD |
title | Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD |
title_full | Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD |
title_fullStr | Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD |
title_full_unstemmed | Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD |
title_short | Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD |
title_sort | oxidative stress decreases functional airway mannose binding lectin in copd |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4047017/ https://www.ncbi.nlm.nih.gov/pubmed/24901869 http://dx.doi.org/10.1371/journal.pone.0098571 |
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