Author: ["Ingrid Hrachovinová","Beatrice Cambien","Ali Hafezi-Moghadam","János Kappelmayer","Raymond T Camphausen","Angela Widom","Lijun Xia","Haig H Kazazian Jr","Robert G Schaub","Rodger P McEver","Denisa D Wagner"]
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Abstract
High plasma levels of soluble P-selectin are associated with thrombotic disorders and may predict future cardiovascular events. Mice with high levels of soluble P-selectin have more microparticles in their plasma than do normal mice. Here we show that chimeras of P-selectin and immunoglobulin (P-sel–Ig) induced formation of procoagulant microparticles in human blood through P-selectin glycoprotein ligand-1 (PSGL-1; encoded by the Psgl1 gene, officially known as Selpl). In addition, Psgl1−/− mice produced fewer microparticles after P-sel–Ig infusion and did not spontaneously increase their microparticle count in old age as do wild-type mice. Injected microparticles specifically bound to thrombi and thus could be involved in thrombin generation at sites of injury. Infusion of P-sel–Ig into hemophilia A mice produced a 20-fold increase over control immunoglobulin in microparticles containing tissue factor. This significantly improved the kinetics of fibrin formation in the hemophilia A mice and normalized their tail-bleeding time. P-sel–Ig treatment could become a new approach to sustained control of bleeding in hemophilia.Cite this article
Hrachovinová, I., Cambien, B., Hafezi-Moghadam, A. et al. Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nat Med 9, 1020–1025 (2003). https://doi.org/10.1038/nm899 