beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway

Abstract

The general hypothesis for the biological function of beta 2- glycoprotein I is that it neutralizes all negatively charged macromolecules that might enter the bloodstream and diminishes unwanted activation of the blood coagulation. In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. Activation was accomplished by an ellagic acid-phospholipid suspension (Cephotest) and measured by the appearance of amidolytic activity using the chromogenic substrate H-D-Pro-Phe-Arg-p-nitroanilide (S-2302). This inhibitory effect of beta 2-glycoprotein I was observed both when Cephotest was preincubated with beta 2-glycoprotein I and when the amount of beta 2- glycoprotein I in plasma was increased by addition of beta 2- glycoprotein I to either normal or beta 2-glycoprotein I-deficient plasma. The inhibitory effect of beta 2-glycoprotein I on the contact phase activation could be one of the physiological functions of this protein.

Autoantibodies in Argentine Women with Recurrent Pregnancy Loss

“…In animal studies anticardiolipin antibodies have a direct effect on fecundity and on the outcome of pregnancy in the pregnant mice 25,26 . Highly purified anticardiolipin antibodies bound to β 2 ‐glycoprotein I ( β 2 GPI), which is a heavily glycosylated 50‐kDa anionic phospholipid binding protein 27 . The physiological functions of this glycoprotein are not totally known.…”

Anti–β2‐glycoprotein I antibodies in pediatric systemic lupus erythematosus and antiphospholipid syndrome

“…Evidence suggests that β 2 GPI may be necessary for the binding of particular aPL to phospholipids and may actually represent the true target of aPL. The physiologic function of β 2 GPI is not known; however, in vitro studies have demonstrated a potential role in anti‐coagulation (1, 2).…”

Genetic risk factors of thrombosis in the antiphospholipid syndrome

“…Although its physiological role is not known, ‘ in vitro ’ data suggest that beta2‐GPI may play a role in coagulation. It binds to anionic phospholipids and inhibits the contact phase of the intrinsic blood coagulation pathway (Schousboe, 1985), adenosine diphosphate–dependent platelet aggregation (Nimpf et al , 1987) and the prothrombinase activity of human platelets (Nimpf et al , 1986). Although these data imply an anticoagulant role for beta2‐GPI, deficiency of this protein is not a clear risk factor for thrombosis.…”