Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/77192
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Type: | Journal article |
Title: | Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema |
Author: | Mukaro, V. Bylund, J. Hodge, G. Holmes, M. Jersmann, H. Reynolds, P. Hodge, S. |
Citation: | PLoS One, 2013; 8(2):1-10 |
Publisher: | Public Library of Science |
Issue Date: | 2013 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Hoshino, Y. |
Statement of Responsibility: | Violet R. Mukaro, Johan Bylund, Greg Hodge, Mark Holmes, Hubertus Jersmann, Paul N. Reynolds, Sandra Hodge |
Abstract: | We have previously shown that the defective ability of alveolar macrophages (AM) to phagocytose apoptotic cells (‘efferocytosis’) in chronic obstructive pulmonary disease/emphysema (COPD) could be therapeutically improved using the C-type lectin, mannose binding lectin (MBL), although the exact mechanisms underlying this effect are unknown. An S-type lectin, galectin-3, is also known to regulate macrophage phenotype and function, via interaction with its receptor CD98. We hypothesized that defective expression of galectin/CD98 would be associated with defective efferocytosis in COPD and that mechanisms would include effects on cytoskeletal remodeling and macrophage phenotype and glutathione (GSH) availability. Galectin-3 was measured by ELISA in BAL from controls, smokers and current/ex-smokers with COPD. CD98 was measured on AM using flow cytometry. We assessed the effects of galectin-3 on efferocytosis, CD98, GSH, actin polymerisation, rac activation, and the involvement of PI3K (using β-actin probing and wortmannin inhibition) in vitro using human AM and/or MH-S macrophage cell line. Significant decreases in BAL galectin-3 and AM CD98 were observed in BAL from both current- and ex-smoker COPD subjects vs controls. Galectin 3 increased efferocytosis via an increase in active GTP bound Rac1. This was confirmed with β-actin probing and the role of PI3K was confirmed using wortmannin inhibition. The increased efferocytosis was associated with increases in available glutathione and expression of CD98. We provide evidence for a role of airway lectins in the failed efferocytosis in COPD, supporting their further investigation as potential macrophage-targeted therapies. |
Keywords: | Macrophages, Alveolar Bronchoalveolar Lavage Fluid Animals Humans Mice Pulmonary Disease, Chronic Obstructive Pulmonary Emphysema Androstadienes Actins rac1 GTP-Binding Protein Arginase Glutathione Lectins Galectin 3 Smoking Phagocytosis Adult Aged Middle Aged Female Male Phosphatidylinositol 3-Kinases Fusion Regulatory Protein-1 Wortmannin |
Rights: | © 2013 Mukaro 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. |
DOI: | 10.1371/journal.pone.0056147 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0056147 |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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hdl_77192.pdf | Published version | 2.49 MB | Adobe PDF | View/Open |
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