Trends in Immunology
Volume 23, Issue 6, 1 June 2002, Pages 313-320
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Review
Galectins and their ligands: amplifiers, silencers or tuners of the inflammatory response?

https://doi.org/10.1016/S1471-4906(02)02232-9Get rights and content

Abstract

Recent evidence has implicated galectins and their ligands as master regulators of immune cell homeostasis. Whereas some members of this family, such as galectin-3, behave as amplifiers of the inflammatory cascade, others, such as galectin-1, trigger homeostatic signals to shut off T-cell effector functions. These carbohydrate-binding proteins, identified by shared consensus amino acid sequences and affinity for β-galactoside-containing sugars, participate in the homeostasis of the inflammatory response, either by regulating cell survival and signaling, influencing cell growth and chemotaxis, interfering with cytokine secretion, mediating cell–cell and cell–matrix interactions or influencing tumor progression and metastasis. The current wealth of new information promises a future scenario in which individual members of the galectin family or their ligands will be used as powerful anti-inflammatory mediators and selective modulators of the immune 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.

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