Galectin-3 type-C self-association on neutrophil surfaces; The carbohydrate recognition domain regulates cell function
(2018) In Journal of Leukocyte Biology 103(2). p.341-353- Abstract
Galectin-3 is an endogenous β-galactoside-binding lectin comprising a carbohydrate recognition domain (CRD) linked to a collagen-like N-domain. Both domains are required for galectin-3 to induce cellular effects; a C-terminal fragment of galectin-3, galectin-3C, containing the CRD but lacking the N-domain, binds cell surface glycoconjugates but does not induce cellular effects since cross-linking promoted by the N-domain is thought to be required. Instead, galectin-3C is proposed to antagonize the effects of galectin-3 by competing for binding sites. The aim of this study was to investigate the effects of galectin-3C on galectin-3 interactions with human neutrophils. Recombinant galectin-3C inhibited galectin-3-induced production of... (More)
Galectin-3 is an endogenous β-galactoside-binding lectin comprising a carbohydrate recognition domain (CRD) linked to a collagen-like N-domain. Both domains are required for galectin-3 to induce cellular effects; a C-terminal fragment of galectin-3, galectin-3C, containing the CRD but lacking the N-domain, binds cell surface glycoconjugates but does not induce cellular effects since cross-linking promoted by the N-domain is thought to be required. Instead, galectin-3C is proposed to antagonize the effects of galectin-3 by competing for binding sites. The aim of this study was to investigate the effects of galectin-3C on galectin-3 interactions with human neutrophils. Recombinant galectin-3C inhibited galectin-3-induced production of reactive oxygen species in primed neutrophils. Surprisingly, this inhibition was not due to competitive inhibition of galectin-3 binding to the cells. In contrast, galectin-3C potentiated galectin-3 binding, in line with emerging evidence that galectin-3 can aggregate not only through the N-domain but also through the CRD. The cell surface interaction between galectin-3C and galectin-3 was corroborated by colocalization of fluorescently labeled galectin-3 and galectin-3C. Galectin-3C can be generated in vivo through cleavage of galectin-3 by proteases. Indeed, in circulation, galectin-3 and galectin-3C were both attached to the cell surface of neutrophils, which displayed great capacity to bind additional galectin-3 and galectin-3C. In conclusion, galectin-3C enhances galectin-3 binding to neutrophils by nonactivating type-C self-association, in parallel to inhibiting neutrophil activation by galectin-3 (induced by type-N self-association). This implicates type-C self-association as a termination system for galectin-3-induced cell activation, with the purpose of avoiding oxidant-dependent tissue damage.
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- author
- Sundqvist, Martina ; Welin, Amanda ; Elmwall, Jonas ; Osla, Veronica ; Nilsson, Ulf J. LU ; Leffler, Hakon LU ; Bylund, Johan and Karlsson, Anna LU
- organization
- publishing date
- 2018-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Carbohydrate recognition domain, Galectin, Neutrophils, Priming, ROS production
- in
- Journal of Leukocyte Biology
- volume
- 103
- issue
- 2
- pages
- 341 - 353
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- scopus:85040247376
- pmid:29345346
- ISSN
- 0741-5400
- DOI
- 10.1002/JLB.3A0317-110R
- language
- English
- LU publication?
- yes
- id
- b28744cb-9d9a-47d7-a742-89a4bee9d569
- date added to LUP
- 2018-01-17 14:07:50
- date last changed
- 2024-06-10 06:26:43
@article{b28744cb-9d9a-47d7-a742-89a4bee9d569,
abstract = {{<p>Galectin-3 is an endogenous β-galactoside-binding lectin comprising a carbohydrate recognition domain (CRD) linked to a collagen-like N-domain. Both domains are required for galectin-3 to induce cellular effects; a C-terminal fragment of galectin-3, galectin-3C, containing the CRD but lacking the N-domain, binds cell surface glycoconjugates but does not induce cellular effects since cross-linking promoted by the N-domain is thought to be required. Instead, galectin-3C is proposed to antagonize the effects of galectin-3 by competing for binding sites. The aim of this study was to investigate the effects of galectin-3C on galectin-3 interactions with human neutrophils. Recombinant galectin-3C inhibited galectin-3-induced production of reactive oxygen species in primed neutrophils. Surprisingly, this inhibition was not due to competitive inhibition of galectin-3 binding to the cells. In contrast, galectin-3C potentiated galectin-3 binding, in line with emerging evidence that galectin-3 can aggregate not only through the N-domain but also through the CRD. The cell surface interaction between galectin-3C and galectin-3 was corroborated by colocalization of fluorescently labeled galectin-3 and galectin-3C. Galectin-3C can be generated in vivo through cleavage of galectin-3 by proteases. Indeed, in circulation, galectin-3 and galectin-3C were both attached to the cell surface of neutrophils, which displayed great capacity to bind additional galectin-3 and galectin-3C. In conclusion, galectin-3C enhances galectin-3 binding to neutrophils by nonactivating type-C self-association, in parallel to inhibiting neutrophil activation by galectin-3 (induced by type-N self-association). This implicates type-C self-association as a termination system for galectin-3-induced cell activation, with the purpose of avoiding oxidant-dependent tissue damage.</p>}},
author = {{Sundqvist, Martina and Welin, Amanda and Elmwall, Jonas and Osla, Veronica and Nilsson, Ulf J. and Leffler, Hakon and Bylund, Johan and Karlsson, Anna}},
issn = {{0741-5400}},
keywords = {{Carbohydrate recognition domain; Galectin; Neutrophils; Priming; ROS production}},
language = {{eng}},
number = {{2}},
pages = {{341--353}},
publisher = {{John Wiley & Sons Inc.}},
series = {{Journal of Leukocyte Biology}},
title = {{Galectin-3 type-C self-association on neutrophil surfaces; The carbohydrate recognition domain regulates cell function}},
url = {{http://dx.doi.org/10.1002/JLB.3A0317-110R}},
doi = {{10.1002/JLB.3A0317-110R}},
volume = {{103}},
year = {{2018}},
}