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 Gothenburg Sweden;Centre for Analysis and Synthesis Department of Chemistry Lund University Lund Sweden;Department of Laboratory Medicine Section of Microbiology Immunology and Glycobiology Lund University Lund Sweden;Department of Oral Microbiology and Immunology Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden

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 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.

【 授权许可】

CC BY