Galectins: regulators of acute and chronic inflammation

Abstract

Galectins, beta-galactoside-binding animal lectins, are differentially expressed by various immune cells as well as a wide range of other cell types. Extracellularly, galectins are able to exhibit bivalent or multivalent interactions with cell-surface glycans on various immune cells and exert various effects. These include cytokine and mediator production, cell adhesion, apoptosis, and chemoattraction. In addition, they can form lattices with cell-surface glycoprotein receptors, resulting in modulation of receptor functions, including clustering and endocytosis. Intracellularly, galectins can participate in signaling pathways and modulate biologic responses. These include apoptosis, cell differentiation, and cell migration. Thus, a large body of literature indicates that galectins play important roles in the immune and inflammatory responses through regulating the homeostasis and functions of immune cells. The use of mice deficient in individual galectins has provided additional evidence for the contributions of these proteins to these responses. Current research indicates that galectins play important roles in the development of acute inflammation as well as chronic inflammation associated with allergies, autoimmune diseases, atherosclerosis, infectious processes, and cancer. Thus, recombinant proteins or specific galectin inhibitors may be used as therapeutic agents for inflammatory diseases.

Redundant and Antagonistic Functions of Galectin-1, -3, and -8 in the Elicitation of T Cell Responses

“…Gals have arisen as key mediators of the innate and adaptive immune response that participate in several processes, such as host-pathogen interaction, inflammatory and autoimmune disorders, host-versus-graft disease, fetal-maternal tolerance, and self-tolerance maintenance (2). Therefore, how Gals control immune cell homeostasis and the underlying mechanisms are crucial.…”

“…Gals have arisen as important regulators of the immune response (2). Different members of this family have been found in primary and secondary lymphoid organs, as well as in circulating cells, and were shown to modulate several pathological processes, such as autoimmunity, chronic inflammation, infection, and tumor progression (4).…”

“…G alectins (Gals) constitute a family of secreted mammalian lectins with affinity for b-galactosides that bind glycoreceptors on target cells and induce multiple biological activities that include a broad spectrum of cellular responses, such as proliferation, apoptosis, differentiation, adhesion, migration, and cytokine secretion (1,2). Gals are characterized by the presence of conserved carbohydrate-recognition domains (CRDs) and are structurally classified into three subgroups: prototype (one CRD, such as Gal-1, -2, and -7), tandem repeat (two linked CRDs, such as Gal-4, -8, and -9), and chimera (one CRD fused to a nonlectin domain; Gal-3).…”

Presence of galectin-1 in the epidermal and dermal thickening of keloid tissues

“…It has been detected in the cell nucleus, cytoplasm and intracellular and extracellular sides of cell membrane, and can be secreted and found in the extracellular space [31]. Gal-1, like others galectins, participates in signaling pathways and regulates a variety of biological responses including cell growth, cell-cell and cell-matrix adhesion, cell differentiation, migration, proliferation and survival [31][32][33][34] and plays a critical role in inflammation, angiogenesis, and tumor development and progression [27,33,35,36]. In human skin, Gal-1 has been implicated in psoriasis [37,38] and malignant lesions including cutaneous cancer [39], mycosis fungoides [40,41], and melanoma [42], and scarce studies have shown that the expression of Gal-1 is upregulated in keloid tissue [43].…”

“…A protein that has been implicated in the wound healing process [23,24], conversion of fibroblasts into myofibroblasts [24][25][26] and production of ECM components [26], inflammation [27], and generation of galectin-glycan complexes [28][29][30], is galectin-1 (Gal-1). Gal-1 is a member of the galectin family that has high affinity for N-acetylLactosamine (LacNAc) disaccharides in both Nand O-glycans and is differentially expressed by various normal and pathological tissues [31].…”