Asunto(s)
Plaquetas/fisiología , Proteínas Activadoras de GTPasa/genética , Megacariocitos/citología , Regulación hacia Arriba , Animales , Plaquetas/efectos de los fármacos , Diferenciación Celular , Línea Celular , Linaje de la Célula , Células Cultivadas , Proteínas Activadoras de GTPasa/metabolismo , Silenciador del Gen , Humanos , Megacariocitos/efectos de los fármacos , Megacariocitos/metabolismo , Ratones , Selectina-P/farmacología , Agregación Plaquetaria/efectos de los fármacos , Cultivo Primario de Células , Trombina/farmacologíaRESUMEN
Sickle cell disease (SCD) is a monogenic disorder estimated to affect more than three million people worldwide. Acute systemic painful vaso-occlusive episode (VOE) is the primary reason for emergency medical care among SCD patients. VOE may also progress to acute chest syndrome (ACS), a type of acute lung injury and one of the primary reasons for mortality among SCD patients. Recently, P-selectin monoclonal antibodies were found to attenuate VOE in SCD patients and lung vaso-occlusion in transgenic humanized SCD mice, highlighting the therapeutic benefit of P-selectin inhibition in SCD. Here, we use quantitative fluorescence intravital lung microscopy (qFILM) to illustrate that tandem P-selectin-glycoprotein ligand-immunoglobulin (TSGL-Ig) fusion molecule containing four P-selectin binding sites, significantly attenuated intravenous (IV) oxyhemoglobin triggered lung vaso-occlusion in SCD mice. These findings highlight the therapeutic potential of TSGL-Ig in preventing VOE and ACS in SCD.