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- Title
Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A.
- Authors
Hrachovinová, Ingrid; Cambien, Beatrice; Hafezi-Moghadam, Ali; Kappelmayer, János; Camphausen, Raymond T; Widom, Angela; Xia, Lijun; Kazazian, Haig H, Jr; Schaub, Robert G; McEver, Rodger P; Wagner, Denisa D
- 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.
- Publication
Nature medicine, 2003, Vol 9, Issue 8, p1020
- ISSN
1078-8956
- Publication type
Journal Article
- DOI
10.1038/nm899