Novel insights into the inhibitory effects of Galectin-1 on neutrophil recruitment under flow

William Harvey Research Institute, Barts and The London, School of Medicine and Dentistry, Charterhouse Square, London, UK.
Journal of Leukocyte Biology (Impact Factor: 4.29). 07/2008; 83(6):1459-66. DOI: 10.1189/jlb.1207831
Source: PubMed


Galectin-1 (Gal-1) is a beta-galactoside-binding protein endowed with anti-inflammatory properties. The purpose of this study was to investigate the effects of endogenous and exogenous Gal-1 on neutrophil recruitment onto TNF-treated endothelium. The effect of human recombinant (hr)Gal-1 on markers of neutrophil activation (CD11b expression, P-selectin glycoprotein ligand 1, and L-selectin shedding) was also assessed. Gal-1 inhibited the platelet-activating factor-induced increase in CD11b expression in a concentration-dependent manner, as assessed by flow cytometry. To determine the effects of Gal-1 on neutrophil recruitment, an in vitro flow chamber was used: Preincubation of neutrophils with hrGal-1 significantly decreased the extent of capture, rolling, and adhesion on activated endothelial monolayers. This inhibition was shared with the endogenous protein, as knockdown of endothelial Gal-1 using small interfering RNA resulted in a significant increase in the number of cells captured and rolling. To verify the effects of Gal-1 in an in vivo system, intravital microscopy of Gal-1 null mice and their wild-type counterparts was performed. Leukocyte adhesion and emigration were increased significantly in the cremasteric circulation of Gal-1 null mice inflamed with IL-1beta. These findings indicate that Gal-1 functions to limit neutrophil recruitment onto a TNF-treated endothelium, a property that may underline its inhibitory effects in acute inflammation.

Download full-text


Available from: Mauro Perretti
  • Source
    • "Continued leukocyte recruitment might also be caused by malfunctioning of restraining or homeostatic mechanisms. More specifically, a number of endogenous inhibitors of leukocyte recruitment have been described [53], including pentraxin 3 (PTX- 3) [54], developmental endothelial locus-1 (del-1) [55], galectin-1 [56] [57], and growth differentiation factor 15 (GDF-15) [58]. It is therefore reasonable to assume that an inhibition or decreased availability of these factors can contribute to continued leukocyte recruitment. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Atherosclerosis is commonly looked upon as a chronic inflammatory disease of the arterial wall arising from an unbalanced lipid metabolism and a maladaptive inflammatory response. However, atherosclerosis is not merely an inflammation of the vessel wall. In fact, the cardinal signs of unstable atherosclerotic lesions are primarily characteristics of failed resolution of a chronic inflammation. In contrast to acute inflammatory events which are typically self-limiting, atherosclerosis is an unresolved inflammatory condition, lacking the switch from the pro-inflammatory to the pro-resolving phase, the latter characterized by termination of inflammatory cell recruitment, removal of inflammatory cells from the site of inflammation by apoptosis and dead cell clearance, reprogramming of macrophages toward an anti-inflammatory, regenerative phenotype, and finally egress of effector cells and tissue regeneration. Here we present an overview on mechanisms of failed resolution contributing to atheroprogression and deliver a summary of novel therapeutic strategies to restore resolution in inflamed arteries. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Apr 2015 · Seminars in Immunology
    • "Gal-1 is a key regulator of murine CD4 þ CD25 þ Foxp3 regulatory T-cells (Garin et al., 2007) which is essential in suppression of anti-cancer immunity (Orentas et al., 2006). Gal-1 also inhibits the immune response at the level of leukocyte infiltration; it decreases the adhesion and extravasation of lymphocytes and neutrophils through activate dendothelium (Cooper et al., 2008). In addition, Gal-1 expression in tumour cells or the surrounding stroma intimately regulates the function and vitality of infiltrating-Tcells (Gandhi et al., 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Stem cells from human exfoliated deciduous teeth (SHED) and dental pulp stem cells (DPSCs) obtained from the dental pulp of human extracted tooth were cultured and characterized to confirm that these were mesenchymal stem cells. The proliferation rate was assessed using AlamarBlue® cell assay. The differentially expressed genes in SHED and DPSCs were identified using GeneFishing(TM) technique. The proliferation rate of SHED (P < 0.05) was significantly higher than DPSCs while SHED had lesser multiplication rate and shorter population doubling time (0.01429, 60.57 hours) than DPSCs (0.00286, 472.43 hours). Two bands were highly expressed in SHED and three bands in DPSCs. Sequencing analysis revealed these to be TIMP Metallopeptidase Inhibitor 1 (TIMP1), and ribosomal protein s8, (RPS8) in SHED and collagen, type I, alpha 1, (COL1A1), follistatin-like 1 (FSTL1), lectin, galactoside-binding, soluble, 1, (LGALS1) in DPSCs.TIMP1is involved in degradation of the extracellular matrix, cell proliferation and anti-apoptotic function and RPS8 is involved as a rate-limiting factor in translational regulation; COL1A1 is involved in the resistance and elasticity of the tissues; FSTL1is an autoantigen associated with rheumatoid arthritis; LGALS1 is involved in cell growth, differentiation, adhesion, RNA processing, apoptosis and malignant transformation. This along with further protein expression analysis holds promise in tissue engineering and regenerative medicine.
    No preview · Article · May 2014 · Cell Biology International
  • Source
    • "Further investigation into the mechanism revealed that galectin-1 treatment enhanced the susceptibility of T cells to antigen-induced apoptosis, increased T cell adhesion to extracellular matrix, and also inhibited IL-2 secretion from collagen-specific T cell hybridomas [54,56,57]. In addition, galectin-1 functions to limit neutrophil recruitment to TNF-treated endothelium; and leukocyte adhesion and emigration were significantly increased in galectin-1-deficient mice inflamed with IL-1β [69]. In a more recent study, galectin-1-deficient mice exhibited increased susceptibility to CIA, with earlier onset of arthritis and more severe manifestations than the wild type mice [70]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Rheumatoid arthritis (RA) is a complex and common systemic autoimmune disease characterized by synovial inflammation and hyperplasia. Multiple proteins, cells, and pathways have been identified to contribute to the pathogenesis of RA. Galectins are a group of lectins that bind to β-galactoside carbohydrates on the cell surface and in the extracellular matrix. They are expressed in a wide variety of tissues and organs with the highest expression in the immune system. Galectins are potent immune regulators and modulate a range of pathological processes, such as inflammation, autoimmunity, and cancer. Accumulated evidence shows that several family members of galectins play positive or negative roles in the disease development of RA, through their effects on T and B lymphocytes, myeloid lineage cells, and fibroblast-like synoviocytes. In this review, we will summarize the function of different galectins in immune modulation and their distinct roles in RA pathogenesis.
    Full-text · Article · Sep 2013
Show more