Activation of Blood Platelets in a Transgenic Mouse Model of Sickle Cell Disease

Vascular occlusion is the main cause of the morbidity and mortality observed in patients with sickle cell disease (SCD). Platelets and leukocytes are known to be activated in SCD, and likely to contribute to the initiation and propagation of vaso-occlusive events leading to widespread end-organ damage. In this study, we evaluated whether mouse platelets are activated in a transgenic model of sickle-cell disease: homozygous for the deletion of mouse β-globin and containingtransgenes for human βs globin linked to the transgene for human α-globin (NY1DD model). We observed that platelets from NY1DD ‘sickle’ mice were more aggregable to collagen and convulxin. Scanning- electron microscopy revealed that both resting and agonist-stimulated ‘sickle’ platelets were more surface-activated compared to matched controls. More P-selectin positive platelets and platelets expressing activated αIIbβ3 integrin were found in NY1DD mice compared to control mice. Similarly, levels of platelet-leukocyte and platelet-erythrocyte aggregates were significantly higher in sickle mice compared to wild-type controls. Our results show that blood platelets were activated in the NY1DD model of sickle cell disease, suggesting that ‘sickle’ platelets actively contribute to inflammation and vascular occlusion and represent a strong candidate for a therapeutic intervention.