Tandem P-Selectin Glycoprotein Ligand Immunoglobulin Prevents Lung Vaso-Occlusion In Scd Mice

Introduction: Sickle cell disease (SCD) is an autosomal-recessive-genetic disorder, which leads to red blood cell sickling, hemolysis and vaso-occlusion. Acute systemic painful vaso-occlusive crisis (VOC) is the predominant pathophysiology requiring emergency medical care by SCD patients. 10-20% of SCD patients hospitalized with VOC tend to develop acute chest syndrome (ACS), a type of lung injury within next few days, suggesting a role for pulmonary vaso-occlusion in ACS. This epidemiology also provides a window for therapeutic intervention provided treatments to prevent vaso-occlusion are available. Earlier, we have shown that VOC involves entrapment of large neutrophil-platelet aggregates in lung arterioles of SCD mice, which is inhibited following intravenous administration of P-selectin function blocking antibody. Recently, a tandem-P-selectin-glycoprotein-ligand-immunoglobulin (TSGL-Ig) with two P-selectin binding sites in tandem, has been shown to prevent P-selectin-dependent liver injury in mice. Here, we test the ability of TSGL-Ig in attenuating P-selectin dependent lung vaso-occlusion in SCD mice.