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MGI Accession ID: MGI:3583060
J Number: J:99599
Other Accession IDs: Title: Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A.
Authors: Hrachovinova I; Cambien B; Hafezi-Moghadam A; Kappelmayer J; Camphausen RT; Widom A; Xia L; Kazazian HH Jr; Schaub RG; McEver RP; Wagner DD
Journal: Nat Med
Volume: 9
Issue: 8
Date: 2003 Aug
Year: 2003
Pages: 1020-5
Review Status: Peer Reviewed

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.

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