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

• 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. ©2018 Society for Leukocyte Biology

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

Nyckelord

carbohydrate recognition domain

galectin

neutrophils

priming

ROS production

calcium

fluorescein isothiocyanate

galectin 3

galectin 3c

matrix metalloproteinase

proteinase

reactive oxygen metabolite

recombinant galectin 3

recombinant galectin 3c

recombinant protein

reduced nicotinamide adenine dinucleotide phosphate oxidase

serine proteinase

unclassified drug

amino terminal sequence

Article

binding affinity

calcium cell level

calcium signaling

carboxy terminal sequence

cell interaction

cell surface

cellular distribution

circulation

competitive inhibition

controlled study

enzyme activation

ex vivo study

flow cytometry

fluorescence

human

human cell

leukocyte activation

leukocyte adherence

leukocyte function

neutrophil

nonhuman

normal human

oxidative stress

priority journal

protein assembly

protein binding

protein cleavage

protein degradation

protein protein interaction

protein structure

Carbohydrate recognition domain

Galectin

Neutrophils

Priming

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)