Sökning: onr:"swepub:oai:gup.ub.gu.se/174943" >
Lectins Offer New P...
Lectins Offer New Perspectives in the Development of Macrophage-Targeted Therapies for COPD/Emphysema
-
Mukaro, V. R. (författare)
-
- Bylund, Johan, 1975 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
-
Hodge, G. (författare)
-
visa fler...
-
Holmes, M. (författare)
-
Jersmann, H. (författare)
-
Reynolds, P. N. (författare)
-
Hodge, S. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2013-02-18
- 2013
- Engelska.
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
- Relaterad länk:
-
https://journals.plo...
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Nyckelord
- OBSTRUCTIVE PULMONARY-DISEASE; MANNOSE-BINDING LECTIN; T-CELL APOPTOSIS; ALVEOLAR MACROPHAGES; GALECTIN-3; EXPRESSION; AIRWAY; EFFEROCYTOSIS; PHAGOCYTOSIS; RECOGNITION
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
Plos One
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas