Regulation of alternative macrophage activation by galectin-3
(2008) In Journal of Immunology 180(4). p.2650-2658- Abstract
- Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane... (More)
- Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane receptor CD98 and by inhibition of PI3K. Increased galectin-3 expression and secretion is a feature of alternative macrophage activation. IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, classical macrophage activation with LPS inhibits galectin-3 expression and release. Galectin-3 binds to CD98, and exogenous galectin-3 or cross-linking CD98 with the mAb 4F2 stimulates PI3K activation and alternative activation. IL-4-induced alternative activation is blocked by bis-(3-deoxy-3-(3-methoxybenzamido)-beta-D-galactopyranosyl) sulfane, a specific inhibitor of extracellular galectin-3 carbohydrate binding. These results demonstrate that a galectin-3 feedback loop drives alternative macrophage activation. Pharmacological modulation of galectin-3 function represents a novel therapeutic strategy in pathologies associated with alternatively activated macrophages. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1198625
- author
- MacKinnon, Alison C ; Farnworth, Sarah L ; Hodkinson, Philip S ; Henderson, Neil C ; Atkinson, Kirsten M ; Leffler, Hakon LU ; Nilsson, Ulf LU ; Haslett, Christopher ; Forbes, Stuart J and Sethi, Tariq
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 180
- issue
- 4
- pages
- 2650 - 2658
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000253005600081
- scopus:42149161735
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240), Division of Microbiology, Immunology and Glycobiology - MIG (013025200)
- id
- aae7bacc-eb05-4f63-8755-cbe03579f9a8 (old id 1198625)
- alternative location
- http://www.jimmunol.org/cgi/content/full/180/4/2650
- date added to LUP
- 2016-04-01 13:28:10
- date last changed
- 2022-04-14 01:14:38
@article{aae7bacc-eb05-4f63-8755-cbe03579f9a8,
abstract = {{Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane receptor CD98 and by inhibition of PI3K. Increased galectin-3 expression and secretion is a feature of alternative macrophage activation. IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, classical macrophage activation with LPS inhibits galectin-3 expression and release. Galectin-3 binds to CD98, and exogenous galectin-3 or cross-linking CD98 with the mAb 4F2 stimulates PI3K activation and alternative activation. IL-4-induced alternative activation is blocked by bis-(3-deoxy-3-(3-methoxybenzamido)-beta-D-galactopyranosyl) sulfane, a specific inhibitor of extracellular galectin-3 carbohydrate binding. These results demonstrate that a galectin-3 feedback loop drives alternative macrophage activation. Pharmacological modulation of galectin-3 function represents a novel therapeutic strategy in pathologies associated with alternatively activated macrophages.}},
author = {{MacKinnon, Alison C and Farnworth, Sarah L and Hodkinson, Philip S and Henderson, Neil C and Atkinson, Kirsten M and Leffler, Hakon and Nilsson, Ulf and Haslett, Christopher and Forbes, Stuart J and Sethi, Tariq}},
issn = {{1550-6606}},
language = {{eng}},
number = {{4}},
pages = {{2650--2658}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{Regulation of alternative macrophage activation by galectin-3}},
url = {{http://www.jimmunol.org/cgi/content/full/180/4/2650}},
volume = {{180}},
year = {{2008}},
}