Browsing by Author "Pardo, E"

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    Antibodies against galectin-8 in patients with systemic lupus erythematosus
    (SOC MEDICA SANTIAGO, 2006) Pardo, E; Carcamo, C; Massardo, L; Mezzano, V; Jacobelli, S; Gonzalez, A; Soza, A
    Background: The family of lectins known as galectins (galectins 1-14) are involved in the regulation of the immune system and in oncogenesis. During a search for antigens recognized by antibodies produced by a patient with systemic lupus erythematosus described. Aim: To determine the frequency of autoantibodies against galectin-8 in lupus patients compared with healthy controls. Patients and Methods: Galectin-8 was purified from a bacterial expression system and used in immunoblot assays as antigen to screen the sera of 55 SLE patients and matched controls. Disease activity was evaluated using the Mexican Modification of the Systemic Lupus Erythematosus Disease Activity Index (MEX-SLEDAI). Results: Reactivity against galectin-8 was detected in 30% of SLE patients, compared to 7% ofcontrols (p = 0.003). We could not detect any particular SLE manifestation associated to the pressence of these autoantibodies. Conclusion: This is the first description of autoantibodies against galectin-8. Its higher frequency in a patients with SLE suggests a pathogenic role. Further studies are needed to determine their clinical relevance (Rev Med Chile 2006; 134: 159-66).
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    Galectin-8 binds specific beta 1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells
    (ELSEVIER INC, 2006) Carcamo, C; Pardo, E; Oyanadel, C; Bravo Zehnder, M; Bull, P; Caceres, M; Martinez, J; Massardo, L; Jacobelli, S; Gonzalez, A; Soza, A
    Integrin-mediated encounters of T cells with extracellular cues lead these cells to adhere to a variety of substrates and acquire a spread phenotype needed for their tissue incursions. We studied the effects of galectin-8 (Gal-8), beta-galactoside binding lectin, on Jurkat T cells. Immobilized Gal-8 bound alpha 1 beta 1 and alpha 5 beta 1 but not alpha 2 beta 1 and alpha 4 beta 1 and adhered these cells with similar kinetics to immobilized fibronectin (FN). Function-blocking experiments with monoclonal anti-integrin antibodies suggested that alpha 5 beta 1 is the main mediator of cell adhesion to this lectin. Gal-8, but not FN, induced extensive cell spreading frequently leading to a polarized phenotype characterized by an asymmetric lamellipodial protrusion. These morphological changes involved actin cytoskeletal rearrangements controlled by PI3K, Rac-1 and ERK1/2 activity. Gal-8-induced Rac-1 activation and binding to alpha 1 and alpha 5 integrins have not been described in any other cellular system. Strikingly, Gal-8 was also a strong stimulus on Jurkat cells in suspension, triggering ERK1/2 activation that in most adherent cells is instead dependent on cell attachment. In addition, we found that patients with systemic lupus erythematosus (SLE), a prototypic autoimmune disorder, produce Gal-8 autoantibodies that impede both its binding to integrins and cell adhesion. These are the first function-blocking autoantibodies reported for a member of the galectin family. These results indicate that Gal-8 constitutes a novel extracellular stimulus for T cells, able to bind specific beta 1 integrins and to trigger signaling pathways conducive to cell spreading. Gal-8 could modulate a wide range of T cell-driven immune processes that eventually become altered in autoimmune disorders. (C) 2005 Elsevier Inc. All rights reserved.