Galectin

About: Galectin is a research topic. Over the lifetime, 2076 publications have been published within this topic receiving 103409 citations. The topic is also known as: IPR001079 & Galectin.

Galectin-9 mediates neutrophil capture and adhesion in a CD44 and β2 integrin-dependent manner.

Abstract: Neutrophil trafficking is a key component of the inflammatory response. Here, we have investigated the role of the immunomodulatory lectin Galectin-9 (Gal-9) on neutrophil recruitment. Our data indicate that Gal-9 is upregulated in the inflamed vasculature of RA synovial biopsies and report the release of Gal-9 into the extracellular environment following endothelial cell activation. siRNA knockdown of endothelial Gal-9 resulted in reduced neutrophil adhesion and neutrophil recruitment was significantly reduced in Gal-9 knockout mice in a model of zymosan-induced peritonitis. We also provide evidence for Gal-9 binding sites on human neutrophils; Gal-9 binding induced neutrophil activation (increased expression of β2 integrins and reduced expression of CD62L). Intra-vital microscopy confirmed a pro-recruitment role for Gal-9, with increased numbers of transmigrated neutrophils following Gal-9 administration. We studied the role of both soluble and immobilized Gal-9 on human neutrophil recruitment. Soluble Gal-9 significantly strengthened the interaction between neutrophils and the endothelium and inhibited neutrophil crawling on ICAM-1. When immobilized, Gal-9 functioned as an adhesion molecule and captured neutrophils from the flow. Neutrophils adherent to Gal-9 exhibited a spread/activated phenotype that was inhibited by CD18 and CD44 neutralizing antibodies, suggesting a role for these molecules in the pro-adhesive effects of Gal-9. Our data indicate that Gal-9 is expressed and released by the activated endothelium and functions both in soluble form and when immobilized as a neutrophil adhesion molecule. This study paves the way for further investigation of the role of Gal-9 in leukocyte recruitment in different inflammatory settings.

Galectins and Their Ligand Glycoconjugates in the Central Nervous System Under Physiological and Pathological Conditions

Abstract: Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and-9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,-3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. N-glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6-N-acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.

Members of the Galectin Network with Deviations from the Canonical Sequence Signature. 2. Galectin-Related Protein (GRP)

Abstract: Galectin-related protein (GRP) is present in vertebrates Sequence comparisons between GRPs from diverse species reveal an unusually high degree of similarity indicative of a strong positive selection In solution, human and chicken GRPs are monomers irrespective of the presence of the 36-amino-acid-long extension of the core structure at the N-terminus They are devoid of ability to bind lactose due to severe deviations from the respective sequence signature Crystallography disclosed distortion of the binding-site architecture that precludes accommodation of lactose The recent characterization of expression of chicken GRP (C-GRP) enables complete galectin network analysis in this organism When tested in a panel of developing and adult organs, C-GRP presence was detected in bursa of Fabricius Its epithelium and vessels as well as bursal B cells are positive in immunohistochemistry In the B lymphocytes, C-GRP was predominantly cytoplasmic, whereas the chicken tandem-repeat-type galectin, the second member of the galectin family expressed in these cells, was detected at the surface Binding of labeled C-GRP to cells and sections was blocked by heparin These data illustrate disparities in expression and ligand profiles within the galectin family and hereby stimulate interest to perform respective mapping for mammalian GRPs as step to define its physiological function(s)

Galectin Regulation of Host Microbial Interactions

Abstract: Galectins regulate a wide variety of biological processes. However, one of the earliest and most common galectin activities is likely their ability to recognize microbes. Galectin binding to microbes can result in direct microbial killing and activation of host immunity, eventually enhancing the ability of a host to eliminate microbes. However, microbes appear to have also evolved the ability to utilize galectins to enhance host attachment, ultimately leading to increased risk for infection. The ability of galectins to directly engage microbes, coupled with their role in regulating host immune function, positions these carbohydrate binding proteins as key factors that can dictate the consequence of microbial exposure. In this way, galectins represent a highly pleiotropic protein family involved in the regulation of a broad range of host-microbial interactions. A. Introduction Host pathogen interactions fundamentally shape a broad range of biological processes. While products of microbial metabolism can impact a wide variety of host activities, from neurological function to overall metabolism and immune homeostasis (1–3), direct interactions between host and microbes can fundamentally shape microbial flora, impact immune function and often ultimately dictate the likelihood of infectious disease (4). Although host factors can interact with a variety of distinct microbial molecular determinants, cell surface glycans represent the most unique, diverse and rich molecular features that decorate microbes (5, 6). As microbial carbohydrate determinants often completely envelope microbes, these structures often represent the first and most significant molecular signature encountered by a host. As a result, hosts appear to have evolved a variety of immune factors that possess the ability to recognize the distinct carbohydrate signature of a broad range of organisms (6–9). Indeed, many immune populations are defined by the distinct repertoire of glycan binding proteins (GBPs) they express (6–8), strongly suggesting that microbial glycan-host interactions may result in the engagement of specific immune cells and thus shape host immunity in fundamental ways. B. Discovery of Galectins Prior to studies that demonstrated the importance of host recognition of microbial glycans in shaping host immunity, the role of cell surface carbohydrates in general remained elusive for many years (10). However, subsequent studies began demonstrating that glycans can regulate a wide variety of fundamental biological processes (11–13). More specifically, the discovery of GBPs provided a potential mechanism of translating a cell surface glycan code into biologically meaningful outcomes (13). The discovery of mammalian GBPs also provided a mechanism whereby hosts may recognize and therefore respond to distinct microbes through recognition of their unique glycan determinants (5). Indeed, while the vast majority of early studies on GBP function focused primarily on GBP regulation of mammalian cell biology, the ability of GBPs to not only bind microbial glycans, but in some cases, exclusively recognize the glycan determinants of microbes, has become a focus GBP studies (5, 9, 14–19). While the microbial glycan specificity of many of these GBPs remains to be defined, GBP-microbial glycan interactions represent a fundamental aspect of host-microbial interactions. Although the ability of plants to express GBPs was recognized in the 19th century, the potential existence of mammalian GBPs was actually quite controversial for many years. It wasn’t until Ashwell and Morrell observed that desiaylated proteins were rapidly cleared in the liver that a potential mammalian GBP activity and therefore target was identified (20). Subsequent studies identified the potential receptor responsible for the removal of desialylated glycoproteins and in so doing characterized the asialoglycoprotein receptor (21, 22), the first example of a mammalian GBP. Despite the fact that the actual function of the asialoglycoprotein receptor would not be recognized until decades later (11), this discovery launched efforts by several labs to determine whether additional GBPs exist in vertebrates. Using similar biochemical approaches, in 1975 Teichberg and colleagues isolated the next vertebrate GBP described from the electric organ of the electric eel Electrophorus electricus (23). Coined electrolectin, the electric eel GBP was the first galectin discovered and was soon followed thereafter by similar proteins isolated by the laboratories of BarMINIREVIEW doi: 10.4052/tigg.1738.1SE (Article for special issue on Galectins)