Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.

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...

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Autores principales:	Violet R Mukaro, Johan Bylund, Greg Hodge, Mark Holmes, Hubertus Jersmann, Paul N Reynolds, Sandra Hodge
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/58442b7977224fb8ac2766c1c3df0349
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spelling	oai:doaj.org-article:58442b7977224fb8ac2766c1c3df03492021-11-18T07:57:13ZLectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.1932-620310.1371/journal.pone.0056147https://doaj.org/article/58442b7977224fb8ac2766c1c3df03492013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23441163/?tool=EBIhttps://doaj.org/toc/1932-6203We 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.Violet R MukaroJohan BylundGreg HodgeMark HolmesHubertus JersmannPaul N ReynoldsSandra HodgePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 2, p e56147 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Violet R Mukaro Johan Bylund Greg Hodge Mark Holmes Hubertus Jersmann Paul N Reynolds Sandra Hodge Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.
description	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.
format	article
author	Violet R Mukaro Johan Bylund Greg Hodge Mark Holmes Hubertus Jersmann Paul N Reynolds Sandra Hodge
author_facet	Violet R Mukaro Johan Bylund Greg Hodge Mark Holmes Hubertus Jersmann Paul N Reynolds Sandra Hodge
author_sort	Violet R Mukaro
title	Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.
title_short	Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.
title_full	Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.
title_fullStr	Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.
title_full_unstemmed	Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.
title_sort	lectins offer new perspectives in the development of macrophage-targeted therapies for copd/emphysema.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/58442b7977224fb8ac2766c1c3df0349
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Lectins offer new perspectives in the development of macrophage-targeted therapies for COPD/emphysema.

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