Galectins and Immune Responses—Just How Do They Do Those Things They Do?

Thiemann, Sandra; Baum, Linda G.

doi:10.1146/annurev-immunol-041015-055402

Cited by 207 publications

(165 citation statements)

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“…After being secreted galectins bind to glycoprotein targets, forming galectin–glycan complexes that regulate the organization of glycosylated receptors as well as their internalization and signaling (Rabinovich and Croci, 2012; Thiemann and Baum, 2016). Thus, they are able to stimulate different signaling cascades associated with inflammation (Norling et al, 2009; Rabinovich and Toscano, 2009; Blidner et al, 2015) and regulate the activity of immune cells by controlling the function of relevant glycosylated receptors.…”

Section: The Inflammatory Response and Its Resolutionmentioning

confidence: 99%

Resolution of Cochlear Inflammation: Novel Target for Preventing or Ameliorating Drug-, Noise- and Age-related Hearing Loss

Kalinec

Lomberk

Urrutia

et al. 2017

Front. Cell. Neurosci.

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A significant number of studies support the idea that inflammatory responses are intimately associated with drug-, noise- and age-related hearing loss (DRHL, NRHL and ARHL). Consequently, several clinical strategies aimed at reducing auditory dysfunction by preventing inflammation are currently under intense scrutiny. Inflammation, however, is a normal adaptive response aimed at restoring tissue functionality and homeostasis after infection, tissue injury and even stress under sterile conditions, and suppressing it could have unintended negative consequences. Therefore, an appropriate approach to prevent or ameliorate DRHL, NRHL and ARHL should involve improving the resolution of the inflammatory process in the cochlea rather than inhibiting this phenomenon. The resolution of inflammation is not a passive response but rather an active, highly controlled and coordinated process. Inflammation by itself produces specialized pro-resolving mediators with critical functions, including essential fatty acid derivatives (lipoxins, resolvins, protectins and maresins), proteins and peptides such as annexin A1 and galectins, purines (adenosine), gaseous mediators (NO, H2S and CO), as well as neuromodulators like acetylcholine and netrin-1. In this review article, we describe recent advances in the understanding of the resolution phase of inflammation and highlight therapeutic strategies that might be useful in preventing inflammation-induced cochlear damage. In particular, we emphasize beneficial approaches that have been tested in pre-clinical models of inflammatory responses induced by recognized ototoxic drugs such as cisplatin and aminoglycoside antibiotics. Since these studies suggest that improving the resolution process could be useful for the prevention of inflammation-associated diseases in humans, we discuss the potential application of similar strategies to prevent or mitigate DRHL, NRHL and ARHL.

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Section: The Inflammatory Response and Its Resolutionmentioning

confidence: 99%

Resolution of Cochlear Inflammation: Novel Target for Preventing or Ameliorating Drug-, Noise- and Age-related Hearing Loss

Kalinec

Lomberk

Urrutia

et al. 2017

Front. Cell. Neurosci.

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“…To avoid any redundancy in the TIGG galectin special issue, I do not intend to completely cover the proposed functions of galectin-3 in innate immunity and host-pathogen interactions, which has been extensively explored and reviewed over several years (18,(24)(25)(26)(27)(28). Instead, the focus of the current review is on the interactions between galec- …”

Section: A Galectins Accumulate In the Cytosol: Distinct Segregationmentioning

confidence: 99%

Cytosolic Galectins and Their Release and Roles as Carbohydrate-Binding Proteins in Host–Pathogen Interaction

Sato

2018

TIGG

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The glycocalyx is a layer of glycoconjugates found on the surface of both host cells and microorganisms. Information presented on some of the glycans on glycoconjugates is recognized by mammalian glycan-binding proteins, lectins, and these interactions modulate various physiological processes, including host innate immune responses. Lectins and host glycoconjugates are synthesized in the same secretory pathway. One notable exception is a family of soluble β-galactoside-binding lectins, galectins, which are synthesized and accumulated in the cytosol and thereby segregated from their glycan ligands. In cases where pathogenic infection persists and tissue injury occurs, galectins are passively released from injured cells. In addition, galectins are actively secreted through unconventional secretory pathways by inflammation-activated or differentiating cells. Thus, extracellular emergence of galectins is associated with the presence of pathogenic hazards. Evidence from a series of studies suggests that galectins exert multiple immunological effects. Extracellular galectin-3 acts as a damage-associated molecular pattern (DAMP) and adhesion molecule for neutrophils in lungs to initiate a proinflammatory response and to mediate rapid neutrophil migration in lungs infected with pathogenic microorganisms. In this review, the roles of galectin-3 in initial innate immune responses and resolution are discussed together with a historical overview of research on galectins in the secretory pathway and innate immunology. A. Galectins Accumulate in the Cytosol: Distinct Segregation from Glycan LigandsIn mammalian cells, the majority of glycans, i.e., oligosaccharides and polysaccharides, are covalently linked to either proteins Galectins are soluble, non-glycosylated lectins defined by a conserved carbohydrate recognition domain (CRD) that shows affinity for β-galactoside, especially glycans containing a number of lactosamine residues (Galβ1-4GlcNAc) (2-4). Detailed information on the carbohydrate binding specificity of galectins has been provided in the review by the group of Hirabayashi in the TIGG special issue 'Galectins updated' (5). In humans, 11 galectins have been identified to date (2). These proteins exhibit structural differences in the presentation of CRD (Fig. 1A). Some contain one CRD (prototype) and exist as either monomers or dimers while others (tandem repeats) contain two CRDs connected by a short linker region. Galectin-3 uniquely occurs as a chimeric protein with one CRD at the C-terminus and an additional non-CRD domain at the N-terminus, which is involved in its oligomerization.Upon binding to its glycan ligands, the conformation of galectin-3 appears altered. Subsequently, galectin-3 molecules oligomerize through self-assembly of the non-CRD domains and become multivalent in glycan binding (Fig. 1B) (6-12). In addition to N-terminal-mediated oligomerization, CRD of galectin-3 selfassociates upon binding to its ligands, thereby contributing to positive cooperativity in the formation of multivalency ...

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“…Galectins share a highly conserved carbohydrate-recognition domain (CRD) that is responsible for their high affinity for β-galactosides in glycoconjugates 1. In mammals, 15 members of this protein family have been cloned, and based on their structural organisation classified into three subfamilies: proto, chimaera and tandem repeat types.…”

Section: Introductionmentioning

confidence: 99%