Role of endogenous galectin-1 in regulation of the hemostatic processes

SCHATTNER M; ROMANIUK MA; LAPPONI MJ; ETULAIN J; CARESTIA A; NEGROTTO S; CROCI DO; RABINOVICH GA

Kyoto

Congreso; XXIII Congress of the International Society on Thrombosis and Haemostasis 2011.; 2011

Galectin-1 (Gal-1), is a 14.5-kDa member of the galectin family regulated by a monomer/dimmer equilibrium that preferentially recognizes multiple Gal 1,4GlcNAc (LacNAc) units presented on the branches of N- or O-linked glycans on cell surface or matrix glycoproteins. Gal-1 plays diverse roles in the control of immune responses, inflammation and cancer. In addition, we have recently demonstrated that soluble Gal-1 triggers a variety of platelet activation responses such as aggregation, release of granule contents and formation of mixed platelet-leukocyte aggregates. In this study, we explored the molecular mechanisms involved in platelet activation mediated by Gal-1 (3μM). The results show that Gal-1 promotes intracellular calcium mobilization (Control:1±0.2% vs 25 ± 4% of positive cells, Flow cytometry, n = 3), stimulates the generation of TXB2 (ELISA) (Control: 1.5 ± 1.0 pg / ml vs Gal-1: 9.± 0.3 pg / ml, n = 3) and induces phosphorylation of ERK and p38 kinases, as well as the activation of Akt kinase (WB, n=3). Mass spectrometry studies identified the αIIb subunit of αIIb3 integrin as a putative surface Gal-1 counter-receptor. Using immobilized Gal-1 we determined by confocal microscopy and adhesion assays that this lectin induced platelet adhesion as well as actin polymerization or spreading. Blockade of Src kinases, PKC and PI3K but not MAPK pathway resulted in a marked (>75% of inhibition, p