Functional properties of galectin-3. Beyond the sugar binding.

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Contemporary diseases like diabetes, asthma, atherosclerosis etc. are marked by chronic inflammation, often supported by the activity of different macrophages. Proteins from galectin family were found to contribute to disease pathophysiology. Therefore, there is an intensive interest in understanding different galectin functions. The aim of this thesis was to pin-point specific galectin-3 roles in differently activated macrophages. Additional aim was to understand the mechanism and consequences of galectin-3 ligand binding.
In the first paper galectin-3 endocytosis was studied in a system of differently activated macrophages. We found that inflammatory, M1, and alternatively activated, M2, macrophages have a large capacity to internalize externally added galectin-3, besides expressing and secreting galectin-3. Additionally, we found that galectin-3 does not require the functional carbohydrate recognition domain (CRD) for its endocytosis.
In the second paper we used M2 macrophages to study how galectin-1 directs the endocytosis of hemoglobin-haptoglobin complex. Our results indicated that galectin-1 bound fraction of the complex takes a recycling intracellular route instead of the pathway for degradation.
The third paper shows how certain complex carbohydrate ligands can induce galectin-3 self-association that involves CRD to CRD binding. This “type-C” self-association engages more galectin-3 molecules than there are available glycan ligands and can explain certain biological events that require fast galectin-3 mobilization.
In the fourth paper we tested the inhibitory potential of a few plant products for several galectins. We found that their activity was very weak, hence the search for more potent anti-galectin, perhaps also anti-inflammatory remedies continues.

Details

Authors
  • Adriana Lepur
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area
  • Microbiology in the medical area

Keywords

  • galectin-3, galectin-1, M1 macrophage, M2 macrophage, self-association, fluorescence anisotropy, citrus pectin, galactomannane
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2012 Oct 5
Publisher
  • Department of Laboratory Medicine, Lund University
Print ISBNs978-91-87189-31-9
Publication statusPublished - 2012
Publication categoryResearch

Bibliographic note

Defence details Date: 2012-10-05 Time: 13:00 Place: Belfragesalen BMC D15 Lund External reviewer(s) Name: Schedin-Weiss, Sophia Title: [unknown] Affiliation: Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Novum, Huddinge, Sweden ---

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Related research output

Adriana Lepur, Michael Carlsson, Ruđer Novak, Jerka Dumić, Ulf Nilsson & Hakon Leffler, 2012, In: Biochimica et biophysica acta. 1820, 7, p. 804-818

Research output: Contribution to journalArticle

Adriana Lepur, Emma Salomonsson, Ulf J Nilsson & Hakon Leffler, 2012, In: Journal of Biological Chemistry. 287, 26, p. 21751-21756

Research output: Contribution to journalArticle

Michael Carlsson, Cecilia Cederfur, Viveka Schaar, Crina I A Balog, Adriana Lepur, Franck Touret, Emma Salomonsson, André M Deelder, Mårten Fernö, Håkan Olsson, Manfred Wuhrer & Hakon Leffler, 2011, In: PLoS ONE. 6, 10, e26560.

Research output: Contribution to journalArticle

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