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)