A Novel Biological Activity for Galectin-1

La, Mylinh; Cao, Thong V.; Cerchiaro, Graziela; Chilton, Kathya; Hirabayashi, Jun; Kasai, Ken‐ichi; Oliani, Sônia Maria; Chernajovsky, Yuti; Perretti, Mauro

doi:10.1016/s0002-9440(10)63507-9

Cited by 134 publications

(51 citation statements)

References 44 publications

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“…Galectins have been shown to be able to contribute to regulation of the migration of immune cells. Human recombinant galectin-1 was found to inhibit chemotaxis as well as trans-endothelial migration of PMN in vitro and inhibit interleukin-1β-induced PMN recruitment into the mouse peritoneal cavity [128]. Intravital microscopy analysis demonstrated that it suppresses the leukocyte flux, but not their rolling velocity [128].…”

Section: Regulation Of the Functions Of Immune Cellsmentioning

confidence: 99%

Regulatory Roles of Galectins in the Immune Response

Liu¹

2005

Int Arch Allergy Immunol

177

121

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Galectins are a family of animal lectins with affinity for β-galactosides. They are differentially expressed by various immune cells and their expression levels appear to be dependent on cell differentiation and activation. They can interact with cell-surface and extracellular matrix glycoconjugates (glycoproteins and glycolipids), through lectin-carbohydrate interactions. Through this action, they can promote cell growth, affect cell survival, modulate cell adhesions, and induce cell migration. They appear to do so by binding to different glycoconjugates decorated by suitable saccharides, rather than through specific receptors. Galectins do not have a classical signal peptide and are often localized in intracellular compartments, including the nucleus. Intracellularly, they can regulate cell growth and survival by interacting with cytoplasmic and nuclear proteins, through protein-protein interactions, thereby affecting intracellular signaling pathways. Current research indicates that galectins play important roles in the immune response through regulating the homeostasis and functions of the immune cells.

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Section: Regulation Of the Functions Of Immune Cellsmentioning

confidence: 99%

Regulatory Roles of Galectins in the Immune Response

Liu¹

2005

Int Arch Allergy Immunol

177

121

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“…However, in adults, it is produced by a majority of tissues (8, 48 -50). In the vasculature, Gal-1 is produced by SMC and endothelial cells and is regulated by proinflammatory mediators and cell activation, including changes in vascular cells that allow them to participate in the immune response (10,30,51). In vitro, Gal-1 regulates SMC attachment to laminin and fibronectin in a dose-dependent manner, which subsequently regulates proliferation, migration, adhesion, and spreading of SMCs by means of ␤ 1 -integrins and focal adhesion kinase signaling (8,9,10,23,37,44).…”

mentioning

confidence: 99%

Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension

Case¹,

Irwin²,

Ivester³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary hypertension (PH) is characterized by sustained vasoconstriction, with subsequent extracellular matrix (ECM) production and smooth muscle cell (SMC) proliferation. Changes in the ECM can modulate vasoreactivity and SMC contraction. Galectin-1 (Gal-1) is a hypoxia-inducible beta-galactoside-binding lectin produced by vascular, interstitial, epithelial, and immune cells. Gal-1 regulates SMC differentiation, proliferation, and apoptosis via interactions with the ECM, as well as immune system function, and, therefore, likely plays a role in the pathogenesis of PH. We investigated the effects of Gal-1 during hypoxic PH by quantifying 1) Gal-1 expression in response to hypoxia in vitro and in vivo and 2) the effect of Gal-1 gene deletion on the magnitude of the PH response to chronic hypoxia in vivo. By constructing and screening a subtractive library, we found that acute hypoxia increases expression of Gal-1 mRNA in isolated pulmonary mesenchymal cells. In wild-type (WT) mice, Gal-1 immunoreactivity increased after 6 wk of hypoxia. Increased expression of Gal-1 protein was confirmed by quantitative Western analysis. Gal-1 knockout (Gal-1(-/-)) mice showed a decreased PH response, as measured by right ventricular pressure and the ratio of right ventricular to left ventricular + septum wet weight compared with their WT counterparts. However, the number and degree of muscularized vessels increased similarly in WT and Gal-1(-/-) mice. In response to chronic hypoxia, the decrease in factor 8-positive microvessel density was similar in both groups. Vasoreactivity of WT and Gal-1(-/-) mice was tested in vivo and with use of isolated perfused lungs exposed to acute hypoxia. Acute hypoxia caused a significant increase in RV pressure in wild-type and Gal-1(-/-) mice; however, the response of the Gal-1(-/-) mice was greater. These results suggest that Gal-1 influences the contractile response to hypoxia and subsequent remodeling during hypoxia-induced PH, which influences disease progression.

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“…Such a sensor may be important in dictating the distribution and longevity of Gal-1 signaling. For example, whereas Gal-1 induces turnover of neutrophils (3,6,40), inhibits leukocyte chemotaxis and induces immunosuppressive cytokine secretion in both naive and activated T cells (40,61), premature engagement of infiltrating leukocyte by Gal-1 could ameliorate an otherwise productive and necessary inflammatory response. The highly oxidative environment surrounding inflammation likely facilitates the oxidation of Gal-1 released during primary tissue injury prior to significant leukocyte recruitment (1), allowing leukocytes to successfully neutralize pathogen or remove necrotic tissue without being impeded by the immunosuppressive effects of Gal-1.…”

Section: Discussionmentioning

confidence: 99%

Ligand Reduces Galectin-1 Sensitivity to Oxidative Inactivation by Enhancing Dimer Formation

Stowell

Cho

Feasley

et al. 2009

Journal of Biological Chemistry

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Galectin-1 (Gal-1) regulates leukocyte turnover by inducing the cell surface exposure of phosphatidylserine (PS), a ligand that targets cells for phagocytic removal, in the absence of apoptosis. Gal-1 monomer-dimer equilibrium appears to modulate Gal-1-induced PS exposure, although the mechanism underlying this regulation remains unclear. Here we show that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidation. A mutant form of Gal-1, containing C2S and V5D mutations (mGal-1), exhibits impaired dimerization and fails to induce cell surface PS exposure while retaining the ability to recognize carbohydrates and signal Ca 2؉ flux in leukocytes. mGal-1 also displayed enhanced sensitivity to oxidation, whereas ligand, which partially protected Gal-1 from oxidation, enhanced Gal-1 dimerization. Continual incubation of leukocytes with Gal-1 resulted in gradual oxidative inactivation with concomitant loss of cell surface PS, whereas rapid oxidation prevented mGal-1 from inducing PS exposure. Stabilization of Gal-1 or mGal-1 with iodoacetamide fully protected Gal-1 and mGal-1 from oxidation. Alkylation-induced stabilization allowed Gal-1 to signal sustained PS exposure in leukocytes and mGal-1 to signal both Ca 2؉ flux and PS exposure. Taken together, these results demonstrate that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidative inactivation and provides a mechanism whereby ligand partially protects Gal-1 from oxidation.Immunological homeostasis relies on efficient contraction of activated leukocytes following an inflammatory episode. Several factors, including members of the galectin and tumor necrosis factor families (1, 2), regulate leukocyte turnover by inducing apoptotic cell death. In contrast, several galectin family members, in particular galectin-1 (Gal-1), 2 uniquely regulate neutrophil turnover by inducing phosphatidylserine (PS) exposure, which normally sensitizes apoptotic cells to phagocytic removal (3, 4), independent of apoptosis, a process recently termed preaparesis (5).Previous studies suggested that dimerization may be required for Gal-1-induced PS exposure, as a mutant form of Gal-1 (mGal-1) containing two point mutations within the dimer interface, C2S and V5D (C2S,V5D), displays impaired Gal-1 dimerization and fails to induce PS exposure (6). However, the manner in which monomer-dimer equilibrium regulates Gal-1 signaling remains unclear. Previous studies suggest that dimerization may be required for efficient cross-linking of functional receptors or the formation of signaling lattices (7-9). Consistent with this, monomeric mutants of several other galectins fail to induce PS exposure or signal leukocytes (4, 8). Gal-1 signaling of PS exposure requires initial signaling events, such as mobilization of intracellular Ca 2ϩ followed by sustained receptor engagement (10). Although mGal-1 fails to induce PS exposure (6), whether mGal-1 can induce these initial signaling events remains unknown (10).In addition to directly regulating signaling, monomer-dimer equilibrium may ...

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A Novel Biological Activity for Galectin-1

Cited by 134 publications

References 44 publications

Regulatory Roles of Galectins in the Immune Response

Regulatory Roles of Galectins in the Immune Response

Mice deficient in galectin-1 exhibit attenuated physiological responses to chronic hypoxia-induced pulmonary hypertension

Ligand Reduces Galectin-1 Sensitivity to Oxidative Inactivation by Enhancing Dimer Formation

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