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

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Martina Sundqvist¹  Amanda Welin¹  Jonas Elmwall¹  Veronica Osla¹  Ulf J. Nilsson²  Hakon Leffler³  Johan Bylund⁴  Anna Karlsson¹ 

[1] Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg;Centre for Analysis and Synthesis, Department of Chemistry, Lund University;Department of Laboratory Medicine, Section of Microbiology, Lund University;Department of Oral Microbiology and Immunology, Sahlgrenska Academy at the University of Gothenburg

关键词: carbohydrate recognition domain;    galectin;    neutrophils;    priming;    ROS production;   

DOI  :  10.1002/JLB.3A0317-110R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Galectin-3 is an endogenous ?-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 galectin3C 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 oxidantdependent tissue damage.

【 授权许可】

CC BY