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Lectins Offer New P...
Lectins Offer New Perspectives in the Development of Macrophage-Targeted Therapies for COPD/Emphysema
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Mukaro, V. R. (author)
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- Bylund, Johan, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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Hodge, G. (author)
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Holmes, M. (author)
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Jersmann, H. (author)
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Reynolds, P. N. (author)
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Hodge, S. (author)
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(creator_code:org_t)
- 2013-02-18
- 2013
- English.
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In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
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Abstract
Subject headings
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- 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 beta-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 beta-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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- OBSTRUCTIVE PULMONARY-DISEASE; MANNOSE-BINDING LECTIN; T-CELL APOPTOSIS; ALVEOLAR MACROPHAGES; GALECTIN-3; EXPRESSION; AIRWAY; EFFEROCYTOSIS; PHAGOCYTOSIS; RECOGNITION
Publication and Content Type
- ref (subject category)
- art (subject category)
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