Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro

J Clin Pathol. 1993 Oct;46(10):908-11. doi: 10.1136/jcp.46.10.908.

Abstract

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.

MeSH terms

  • Antibodies, Antiphospholipid / pharmacology*
  • Apolipoproteins / pharmacology*
  • Blood Coagulation
  • Dose-Response Relationship, Drug
  • Female
  • Glycoproteins / pharmacology*
  • Humans
  • Immunoglobulin G / immunology
  • In Vitro Techniques
  • Male
  • Protein Binding
  • Protein C / antagonists & inhibitors*
  • Protein C / metabolism
  • beta 2-Glycoprotein I

Substances

  • Antibodies, Antiphospholipid
  • Apolipoproteins
  • Glycoproteins
  • Immunoglobulin G
  • Protein C
  • beta 2-Glycoprotein I