A novel role for Galectin-8 as an activator of human platelets

MARÍA VIRGINIA TRIBULATTI, ALBERTINA ROMANIUK, VALENTINA CATTANEO, JULIA ETULAIN, OSCAR CAMPETELLA, MIRTA SCHATTNER

San Diego, California, Estados Unidos

Conferencia; Annual Conference of the Society for Glycobiology; 2009

Society for Glycobiology

Galectins are mammalian lectins with affinity to beta-galactosides. Galectin-8 (Gal-8) belongs to the tandem-repeat group, containing two distinct carbohydrate recognition domains joined by a linker peptide. We have previously determined by MALDI-MS that Gal-8 binds to integrin alpha IIb in mouse platelets. Considering that this integrin is part of the glycoproteic complex IIbIIIa which is the most relevant molecule in platelet function, we now evaluated the effect of Gal-8 in human platelet physiology. Results obtained demonstrate that human platelets not only expressed Gal-8 but also released it after activation with thrombin. Addition of recombinant L and M isoforms was able to induce platelet activation through outside-in and inside-out signaling. Gal-8 promoted platelet aggregation and exacerbated the response induced by other platelet agonists. Release of von Willebrand factor and ATP from alpha and dense granules, respectively, was also induced. Platelet aggregation response was inhibited with lactose, indicating that Gal-8 effects rely upon interaction with surface glycans. The absence of activation in platelets preincubated with EDTA or Aspirin showed that the observed response is not an agglutination phenomenon and that it does not involve thromboxane generation. Flow cytometry studies demonstrated that Gal-8 promotes intracellular calcium mobilization and expression of neoepitopes in the glycoproteic complex IIbIIIa as well as fibrinogen binding and P-selectin exposure. Finally, Gal-8 triggered MAPKinase activation pathway in platelets as seen by ERK phosphorylation induction. These data together with the known expression of Gal-8 by the endothelium, reveal this lectin as an important physiological modulator of platelet function