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Publication Detail
Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Keeling DM, Wilson AJ, Mackie IJ, Isenberg DA, Machin SJ
  • Publication date:
  • Pagination:
    908, 911
  • Journal:
    J Clin Pathol
  • Volume:
  • Issue:
  • Status:
  • Country:
  • Print ISSN:
  • Language:
  • Keywords:
    Antibodies, Antiphospholipid, Apolipoproteins, Blood Coagulation, Dose-Response Relationship, Drug, Female, Glycoproteins, Humans, Immunoglobulin G, In Vitro Techniques, Male, Protein Binding, Protein C, beta 2-Glycoprotein I
AIMS: To investigate the effect of beta 2-glycoprotein I (beta 2 GPI) on the thrombin/thrombomodulin dependent activation of protein C; and to determine whether beta 2 GPI dependent anticardiolipin antibodies have any effect. METHODS: Protein C was activated by thrombin in the presence of thrombomodulin and phospholipid vesicles in an in vitro system. The effect of adding purified beta 2 GPI to this system was observed. Affinity purified anticardiolipin antibodies and total IgG from patients with anticardiolipin antibodies and the lupus anticoagulant were studied for their effects on protein C activation in the presence and absence of beta 2 GPI. RESULTS: beta 2-Glycoprotein I had no effect on the activity of preformed activated protein C. When the phospholipid vesicles were incubated with beta 2 GPI before the addition of protein C, the activation of protein C was inhibited in a dose dependent manner. With phosphatidylserine:phosphatidylcholine vesicles at a concentration of 1 microM:2 microM, beta 2 GPI began to inhibit the reaction at a concentration of 15 nM, and at 4 microM (the normal plasma concentration) the activation of protein C was reduced to 40%. Anticardiolipin antibodies had no demonstrable effect. CONCLUSIONS: beta 2-Glycoprotein I inhibits protein C activation in an in vitro system. Its physiological role is unknown but it has potential procoagulant as well as anticoagulant properties. An effect of antiphospholipid antibodies on protein C activation, which might explain their association with thrombosis, could not be shown.
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