The influence of anti-endothelial/antiphospholipid antibodies on fibrin formation and lysis on endothelial cells

Angela Margaret Patterson, Isobel Ford, Audrey Graham, Nuala Booth, Michael Greaves

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

The prothrombotic mechanisms associated with antiphospholipid antibodies remain incompletely defined. Antibody binding to endothelial cells in vitro is a feature of antiphospholipid antibody-positive sera. We hypothesised that impairment of endothelium-dependent fibrinolysis by antiphospholipid/anti-endothelial antibodies is a contributory factor in the pathogenesis of thrombosis. We also aimed to confirm the displacement of annexin-V from endothelial cells and enhanced fibrin formation. Binding of immunoglobulin (Ig) from antiphospholipid antibody-positive sera to endothelial cells was examined using a cell-based enzyme-linked immunosorbent assay. Effects on fibrin formation and lysis were examined on cultured endothelial cell monolayers. Plasminogen activator inhibitor-1 (PAI-1) was assayed in supernatants. We confirmed antibody binding to endothelial cells. With four of 14 antiphospholipid antibody-positive sera there was some prolongation of fibrin clot lysis time, consistent with impairment of endothelial fibrinolytic activity. Secretion of PAI-1 was significantly correlated with clot lysis time on endothelial cell monolayers incubated with antiphospholipid/anti-endothelial antibody-positive sera, but not with control sera. IgG from antiphospholipid antibody-positive sera had little effect on endothelial cell surface annexin-V expression. We conclude that impaired endothelial fibrinolysis is a potential prothrombotic mechanism in subjects with antiphospholipid antibodies. We were unable to confirm enhanced displacement of annexin-V from endothelium by antiphospholipid antibodies.

Original languageEnglish
Pages (from-to)323-330
Number of pages7
JournalBritish Journal of Haematology
Volume133
Issue number3
Early online date10 Feb 2006
DOIs
Publication statusPublished - May 2006

Keywords

  • anti-endothelial antibody
  • antiphospholipid antibody
  • fibrinolysis
  • primary antiphospholipid syndrome
  • systemic lupus-erythematosus
  • annexin-v
  • anticardiolipin antibodies
  • tissue factor
  • thrombogenic mechanism
  • protein-C
  • thrombosis
  • binding
  • membranes

Cite this