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Galectin-3 type-C self-association on neutrophil surfaces; The carbohydrate recognition domain regulates cell function

Sundqvist, Martina; Welin, Amanda; Elmwall, Jonas; Osla, Veronica; Nilsson, Ulf J. LU ; Leffler, Hakon LU ; Bylund, Johan and Karlsson, Anna LU (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
organization
publishing date
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
Society for Leukocyte Biology
external identifiers
  • scopus:85040247376
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
2018-02-19 01:48:38
@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},
  keyword      = {Carbohydrate recognition domain,Galectin,Neutrophils,Priming,ROS production},
  language     = {eng},
  number       = {2},
  pages        = {341--353},
  publisher    = {Society for Leukocyte Biology},
  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},
  volume       = {103},
  year         = {2018},
}