Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A

Ingrid Hrachovinová, Beatrice Cambien, Ali Hafezi-Moghadam, János Kappelmayer, Raymond T. Camphausen, Angela Widom, Lijun Xia, Haig H. Kazazian, Robert G. Schaub, Rodger P. McEver, Denisa D. Wagner

Research output: Contribution to journalArticle

241 Citations (Scopus)

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 Psgi1 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.

Original languageEnglish
Pages (from-to)1020-1025
Number of pages6
JournalNature medicine
Volume9
Issue number8
DOIs
Publication statusPublished - Aug 1 2003

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Hrachovinová, I., Cambien, B., Hafezi-Moghadam, A., Kappelmayer, J., Camphausen, R. T., Widom, A., Xia, L., Kazazian, H. H., Schaub, R. G., McEver, R. P., & Wagner, D. D. (2003). Interaction of P-selectin and PSGL-1 generates microparticles that correct hemostasis in a mouse model of hemophilia A. Nature medicine, 9(8), 1020-1025. https://doi.org/10.1038/nm899