GALECTIN-1 BINDING TO PLATELETS: A NEW MECHANISM FOR PLATELET ACTIVATION

M. SCHATTNER; N. PACIENZA; R. POZNER; G.A. BIANCO; L. DÀTRI; S NEGROTTO; E MALAVER; R GOMEZ; G. RABINOVICH

GINEBRA, SUIZA

Congreso; ANNUAL MEETING OF THE INTERNATIONAL ASSOCIATION OF THROMBOSIS AND HEMOSTASIS; 2007

INTERNATIONAL ASSOCIATION OF THROMBOSIS AND HEMOSTASIS

Galectin-1 binding to platelets: a new mechanism for platelet activation. Schattner M, Pacienza N1, Pozner RG1 , Bianco G, D´Atri LP1, Negrotto S1,Malaver E1, Gómez RM2, and Rabinovich G. 1Academy of Medicine, Buenos Aires2, University of La Plata, La Plata, 3 Faculty of Medicine, Buenos Aires, Argentina. Introduction: Galectin-1 (Gal-1) is a lectin present in a wide range of cell types with important functions in immunity and inflammation. Beyond a relevant role in hemostasis and thrombosis, platelets also participate in the regulation of inflammatory and immune responses. Since limited information is available on how Gal-1 may impact platelets, we examined whether platelets contain Gal-1 and the effect of human recombinant Gal-1 on platelet function. Methods: Platelet aggregation was measured by the turbidimetric method; alpha membrane granule proteins expression, conformational changes in GPIIbIIIa, microparticles and platelet-leukocyte interactions by flow cytometry. Endogenous Gal-1 was evaluated by Western blotting. Results: Gal-1 triggered different platelet activation responses including aggregation, PAC-1 binding, P-selectin and GPIIIa expression, shedding of microvesicles and formation of PMN- or monocyte-platelet aggregates. EDTA or PAPA/NO but not suppression of ciclo-oxigenase or PKC activity inhibited P-selectin expression and microparticles generation. The binding of biotinylated Gal-1 to platelets as well as suppression of all the Gal-1-mediated platelet responses by lactose indicated that Gal-1 effects are mediated through a specific interaction with oligosaccharides in platelet membrane. Furthermore, Western blot studies shown that platelets contain Gal-1 and ADP or adrenaline-induced platelet aggregation was inhibited by lactose or a polyclonal anti-Gal antibody. Our results provide the first evidence of Gal-1 expression in human platelets and reveal a novel unrecognized role for Gal-1 in the control of platelet physiology with potential implications in thrombosis, inflammation and tumor progression.