Vol 9: Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD.Report as inadecuate



 Vol 9: Oxidative Stress Decreases Functional Airway Mannose Binding Lectin in COPD.


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This article is from PLoS ONE, volume 9.AbstractWe 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′-azobis2-methylpropionamidinedihydrochroride 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.



Author: Tran, Hai B.; Ahern, Jessica; Hodge, Greg; Holt, Phillip; Dean, Melinda M.; Reynolds, Paul N.; Hodge, Sandra

Source: https://archive.org/







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