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Published VersionCC BY V4.0, Open Access
Journal article
Oxidative stress decreases functional airway mannose binding lectin in COPD
PLoS One, Vol.9(6), pp.1-6
2014
PMCID: PMC4047017
PMID: 24901869
Abstract
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.
Details
- Title
- Oxidative stress decreases functional airway mannose binding lectin in COPD
- Authors
- Hai B Tran (Author) - Royal Adelaide HospitalJessica Ahern (Author) - Royal Adelaide HospitalGreg L Hodge (Author) - The University of AdelaidePhillip Holt (Author) - Royal Adelaide HospitalMelinda M Dean (Author) - Australian Red Cross Blood ServicePaul N Reynolds (Author) - The University of AdelaideSandra Hodge (Author) - The University of Adelaide
- Publication details
- PLoS One, Vol.9(6), pp.1-6
- Publisher
- Public Library of Science
- Date published
- 2014
- DOI
- 10.1371/journal.pone.0098571
- ISSN
- 1932-6203; 1932-6203
- PMID
- 24901869; PMC4047017
- Copyright note
- (c) 2014 Tran et al. 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 credited.
- Organisation Unit
- School of Health - Biomedicine; School of Health and Behavioural Sciences - Legacy
- Language
- English
- Record Identifier
- 99513883702621
- Output Type
- Journal article
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- Domestic collaboration
- Web Of Science research areas
- Respiratory System
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Source: InCites