title: Galectin-8 elicits pro-inflammatory activities in the endothelium.
abstract: Galectins (Gals), a family of mammalian lectins, play diverse roles under physiological and pathological conditions. Here, we analyzed the tandem-repeat Gal-8 synthesis, secretion and effects on the endothelium physiology. Gal-8M and Gal-8L isoforms were secreted under basal conditions by human microvascular endothelial cells (HMEC-1). However, expression and secretion of the Gal-8M isoform, but not Gal-8L, were increased in response to bacterial lipopolysaccharide (LPS) stimulus and returned to control values after LPS removal. Similarly, cell surface Gal-8 exposure was increased after stimulation with LPS. To evaluate Gal-8 effects on the endothelium physiology, HMEC-1 cells were incubated in the presence of recombinant Gal-8M. Pretreated HMEC-1 cells became proadhesive to human normal platelets, indicating that Gal-8 actually activates endothelial cells. This effect was specific for lectin activity as it was prevented by the simultaneous addition of lactose, but not by sucrose. Endothelial cells also increased their exposition of von Willebrand factor after Gal-8 treatment, which constitutes another feature of cell activation that could be, in turn, responsible for the observed platelet adhesion. Several pro-inflammatory molecules were abundantly produced by Gal-8 stimulated endothelial cells: CXCL1 (GRO-α), GM-CSF, IL-6 and CCL5 (RANTES), and in a lower degree CCL2 (MCP-1), CXCL3 (GRO-γ) and CXCL8 (IL-8). In agreement, Gal-8M induced nuclear factor kappa B phosphorylation. Altogether, these results not only confirm the pro-inflammatory role we have already proposed for Gal-8 in other cellular systems but also suggest that this lectin is orchestrating the interaction between leukocytes, platelets and endothelial cells.
authors: Laboratorio de Inmunología Molecular, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomus (IIB-INTECH), Universidad Nacional de San Martín-Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín B1650HMP, Buenos Aires, Argentina;
authors: Valentina
authors: V
authors: Cattaneo
authors: Laboratorio de Inmunología Molecular, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomus (IIB-INTECH), Universidad Nacional de San Martín-Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín B1650HMP, Buenos Aires, Argentina;
authors: María Virginia
authors: MV
authors: Tribulatti
authors: Laboratorio de Inmunología Molecular, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomus (IIB-INTECH), Universidad Nacional de San Martín-Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín B1650HMP, Buenos Aires, Argentina;
authors: Julieta
authors: J
authors: Carabelli
authors: Laboratorio de Trombosis Experimental, Instituto de Medicina Experimental (IMEX), CONICET-Academia Nacional de Medicina, C1425AUM Ciudad Autónoma de Buenos Aires, Argentina.
authors: Agostina
authors: A
authors: Carestia
authors: Laboratorio de Trombosis Experimental, Instituto de Medicina Experimental (IMEX), CONICET-Academia Nacional de Medicina, C1425AUM Ciudad Autónoma de Buenos Aires, Argentina.
authors: Mirta
authors: M
authors: Schattner
authors: Laboratorio de Inmunología Molecular, Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomus (IIB-INTECH), Universidad Nacional de San Martín-Consejo Nacional de Investigaciones Científicas y Técnicas (UNSAM-CONICET), San Martín B1650HMP, Buenos Aires, Argentina; oscar@iib.unsam.edu.ar ocampetella@gmail.com.
authors: Oscar
authors: O
authors: Campetella
mesh_terms: D004727:Endothelium / Q000378:metabolism*; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000737:chemistry; D020080:Tandem Repeat Sequences / Q000235:genetics
chemical_list: D037161:Galectins; D016209:Interleukin-8; C091991:LGALS8 protein, human; D008070:Lipopolysaccharides
keywords: endothelial cell; galectin-8; inflammation; platelets