Trends in Immunology
ReviewGalectins and their ligands: amplifiers, silencers or tuners of the inflammatory response?
Section snippets
Galectins in T-cell homeostasis and survival
Primary selection of the T-cell repertoire occurs within the thymus, but significant fine-tuning of the repertoire can also occur in the periphery, as a result of preferential expansion or contraction of T-cell populations in response to homeostatic signals. Although the mechanisms regulating T-cell homeostasis and survival are not fully understood, it is well-known that a variety of signals can trigger or block cell death and proliferation.
Galectin-1 has recently emerged as an important
Galectins modulate cell–cell and cell–matrix interactions
In addition to the role of galectins in cell growth and survival, these lectins can potentiate or inhibit cell–cell and cell–matrix interactions (reviewed in Ref. [3]). Galectin-1 and -3 have both pro-adhesive and anti-adhesive properties, regulated by binding of saccharide ligands on cell surface glycoproteins and extracellular matrix (ECM) glycoproteins, such as fibronectin and laminin [48]. For example, galectin-1 expressed by thymic epithelial cells mediates the binding of these cells to T
Galectins in T-cell-mediated immune disorders
Through its ability to inhibit T-cell effector functions, galectin-1 has powerful immunoregulatory effects in vivo 54., 55., 56., 57.. Offner et al. provided clinical and histopathological evidence that galectin-1 prevents the development of experimental autoimmune encephalomyelitis in rats [54]. It has been demonstrated that recombinant galectin-1 and its genetic delivery suppress the inflammatory response in collagen-induced arthritis, an experimental model of rheumatoid arthritis [55]. The
Galectins in acute inflammation
In addition to the role of galectins in chronic inflammation, galectins also participate in acute and allergic inflammation (reviewed in Ref. [4]). Galectin-1 ameliorates edema induced by bee venom phospholipase A2, when pre- or co-injected together with the enzyme [64]. Moreover, it inhibits the release of arachidonic acid from lipopolysaccharide (LPS)-stimulated macrophages, neutrophil extravasation and mast-cell degranulation [64].
In contrast to the anti-inflammatory effects of galectin-1,
Galectins in microbial infections
Recent studies have shown that galectin-1 influences the ability of macrophages to control intracellular infections, either by inhibiting microbicidal activity, promoting parasite replication or inducing host-cell apoptosis [72]. Low concentrations of galectin-1 almost completely block IL-12, but not IL-10, production by Trypanosoma cruzi-infected murine-infected macrophages.
Selective inhibition of production of this cytokine is reflected by the enhanced survival and replication of
Galectins in tumor progression and metastasis
Galectins have been shown to be involved in many cellular functions that are crucial during cancer progression and metastasis (reviewed in Refs 76., 77.). For example, both galectin-1 and -3 have been reported to induce the homotypic adhesion of isolated tumor cells by interacting with soluble or membrane-associated ligands 78., 79., 80.. As the survival of blood-borne cancer cells is enhanced by their homotypic adhesion, it is probable that galectin-mediated aggregation of malignant cells
Concluding remarks
The current wealth of new information on the galectin family and their ligands promises a ripe field that will reveal novel mechanisms to control basic cellular processes, such as proliferation, signal transduction and cell death, as well as interesting new possibilities in the diagnosis and treatment of disease in the near future. The study of glycan biosynthesis and glycosylation of cell surface receptors in the course of immunological responses may also help us to understand the multifaceted
Acknowledgements
We apologize to the authors of many relevant references not cited because of space limitations. Gabriel A. Rabinovich thanks Natalia Rubinstein, Marta Toscano, Leonardo Fainboim, Jorge Geffner, Osvaldo Podhajcer, Eduardo Chuluyan, Norberto Zwirner and Jun Hirabayashi for their continuous support.
References (82)
Selectins, T-cell rolling and inflammation
Mol. Med. Today
(1997)Galectins: a new family of regulators of inflammation
Clin. Immunol.
(2000)Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release
J. Biol. Chem.
(2002)Expression of a specific glycosyltransferase enzyme regulates T-cell death mediated by galectin-1
J. Biol. Chem.
(2000)Galectin-3 protects human breast carcinoma cells against nitric-oxide-induced apoptosis: implication of galectin-3 function during metastasis
Am. J. Pathol.
(2001)Galectin-3 overexpression protects from cell damage and death by influencing mitochondrial homeostasis
FEBS Lett.
(2000)Galectin-3 stimulates cell proliferation
Exp. Cell Res.
(1998)Targeted disruption of the galectin-3 gene results in attenuated peritoneal inflammatory responses
Am. J. Pathol.
(2000)Glycosylation, immunity and autoimmunity
Cell
(2001)Cell cycle regulation by galectin-12, a new member of the galectin superfamily
J. Biol. Chem.
(2001)
Phosphorylation of the beta-galactoside-binding protein galectin-3 modulates binding to its ligands
J. Biol. Chem.
Galectin-3 phosphorylation is required for its anti-apoptotic function and cell cycle arrest
J. Biol. Chem.
Recombinant human β-galactoside-binding lectin suppresses clinical and histological signs of experimental autoimmune encephalomyelitis
J. Neuroimmunol.
Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes
J. Biol. Chem.
Galectin-3 activates the NADPH oxidase in exudated but not peripheral-blood neutrophils
Blood
An endogenous lectin, galectin-3 (ε-BP/Mac-2) potentiates IL-1 production by human monocytes
Immunol. Lett.
God must love galectins; he made so many of them
Glycobiology
Galectins: an evolutionarily conserved family of animal lectins with multifunctional properties; a trip from the gene to clinical therapy
Cell Death Differ.
The family of metazoan metal-independent β-galactoside-binding lectins: structure, function and molecular evolution
Glycobiology
Galectin-8: a complex sub-family of galectins
Int. J. Mol. Med.
Galectin-1: secretion and modulation of cell interactions with laminin
Trends Glycosci. Glycotechnol.
Plasma membrane targetting, vesicular budding and release of galectin-3 from the cytoplasm of mammalian cells during secretion
J. Cell Sci.
Galectin-1: oligomeric structure and interactions with polylactosamine
Trends Glycosci. Glycotechnol.
Multivalent protein–carbohydrate interactions. A new paradigm for supermolecular assembly and signal transduction
Biochemistry
Identification of galectin-3 as a factor in pre-mRNA splicing
Proc. Natl. Acad. Sci. U. S. A.
Expression of galectin-3 modulates T-cell growth and apoptosis
Proc. Natl. Acad. Sci. U. S. A.
Human thymic epithelial cells express an endogenous lectin, galectin-1, which binds to core 2 O-glycans on thymocytes and T lymphoblastoid cells
J. Exp. Med.
β-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells
Eur. J. Immunol.
Activated rat macrophages produce a galectin-1-like protein that induces apoptosis of T cells: biochemical and functional characterization
J. Immunol.
Regulated expression of galectin-1 during B-cell activation and implications for T-cell apoptosis
J. Leukoyte Biol.
Specific inhibition of lymphocyte proliferation and induction of apoptosis by CLL-I, a β-galactoside-binding lectin
J. Biochem.
Negative cell cycle control of human T cells by β-galactoside-binding protein (β GBP): induction of programmed cell death in leukaemia cells
J. Cell. Physiol.
Galectin-1, an endogenous lectin produced by thymic epithelial cells, induces apoptosis of human thymocytes
J. Exp. Med.
Apoptosis of T cells mediated by galectin-1
Nature
Galectin-1 specifically modulates TCR signals to enhance TCR apoptosis but inhibit IL-2 production and proliferation
J. Immunol.
Molecular mechanisms implicated in galectin-1-induced apoptosis: activation of the AP-1 transcription factor and downregulation of Bcl-2
Cell Death Differ.
CD45 modulates galectin-1-induced T-cell death: regulation by expression of core 2 O-glycans
J. Immunol.
Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1
J. Immunol.
Cited by (504)
Advances in the green extraction methods and pharmaceutical applications of bioactive pectins from unconventional sources: a review
2022, Studies in Natural Products ChemistryLGALS3BP/Gal-3 promotes osteogenic differentiation of human periodontal ligament stem cells
2021, Archives of Oral BiologyGalectin-3 Impairs Calcium Transients and β-Cell Function
2024, Research Square