Phosphatidylserine expression on cell surfaces promotes antibody-dependent aggregation and thrombosis in β2-glycoprotein I-immune mice

Derek Dombroski, Krishnakumar Balasubramanian, Alan J. Schroit

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Beta-2-glycoprotein I (β2GP1) has been implicated as the primary antigenic target in antiphospholipid syndrome. To study the role β2GP1 antibodies play in thrombosis associated with this syndrome, the clearance and binding of phosphatidylserine (PS)-containing target membranes were monitored in β2GP1-immune mice. Clearance in immune mice (T(1/2)4.8 min) was faster than in normal mice (T(1/2) 11.0 min). Analysis of PS vesicles recovered from immune mice by sequencing and Western blotting showed the presence of bound β2GP1 and autologous antibody, respectively. Bleeding times in immune mice were ~30% shorter than in control mice. In vitro clotting times, however, were the same in both populations. To determine if the in vivo results could be attributed to the interaction of autoantibodies with the vascular endothelium, the binding of PS-containing target membranes to normal and apoptotic endothelial cells was studied. While endothelial cells bound PS vesicles, β2GP1 reduced uptake by ~50% in both normal and apoptotic endothelium. In the presence of β2GP1 antibodies, however, uptake in apoptotic cells, but not normal cells, increased by more than two-fold. These results suggest that thrombosis in antiphospholipid syndrome could, in part, be due to antibody-dependent cross-linking of β2GP1 bound to PS-expressing cells and the vascular endothelium. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)221-229
Number of pages9
JournalJournal of Autoimmunity
Volume14
Issue number3
DOIs
StatePublished - Jan 1 2000

Keywords

  • Antiphospholipid syndrome
  • Apoptosis
  • Beta-2-glycoprotein I
  • Phosphatidylserine
  • Thrombosis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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