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

Schousboe, Inger

doi:10.1182/blood.v66.5.1086.1086

Cited by 333 publications

(55 citation statements)

References 30 publications

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“…2 -GPI/aCL is thought to be directed against a complex that includes cardiolipin and 2 -GPI [10], which raises the possibility that 2 -GPI/aCL may interfere with 2 -GPI function in vivo. Since 2 -GPI inhibits the intrinsic pathway of coagulation [7], ADPmediated platelet aggregation [8], and prothrombinase activity of activated platelets [9], one dominant function of 2 -GPI in vivo may be to diminish the hypercoagulation to form a complex with anionic phospholipids such as cardiolipin present on plasma membranes of injured or activated endothelial cells. Anionic phospholipids, which are normally located inside cell membranes, may undergo transbilayer movement when the cells are injured or activated.…”

Section: Discussionmentioning

confidence: 99%

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Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β2-GPI) in systemic sclerosis

Ihn

Sato

Fujimoto

et al. 1996

Clinical and Experimental Immunology

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SUMMARYIn order to determine the prevalence and clinical significance of¯2-GPI-dependent anticardiolipin antibodies (¯2-GPI/aCL) in patients with systemic sclerosis (SSc), serum samples from 80 patients with SSc, 20 patients with systemic lupus erythematosus (SLE), and 120 healthy control subjects were examined by ELISA using purified¯2-GPI. IgG isotype¯2-GPI/aCL was present in eight of 80 patients with SSc (10%), and the presence of¯2-GPI/aCL IgG was significantly correlated with the presence of isolated pulmonary hypertension (PH). Furthermore, levels of¯2-GPI/aCL IgG were significantly correlated with levels of mean pulmonary arterial pressure. These data suggest that IgG isotype¯2-GPI/ aCL might be a serological indicator of the severity of PH in patients with SSc.

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Section: Discussionmentioning

confidence: 99%

“…This cofactor was identified as 2 -GPI (also called apolipoprotein H) [6]. Various physiological functions of 2 -GPI have been reported: inhibition of the intrinsic coagulation pathway [7], of adenosine diphosphate (ADP)-mediated platelet aggregation [8], and of prothrombinase activity of activated platelets [9].…”

Section: Introductionmentioning

confidence: 99%

Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β2-GPI) in systemic sclerosis

Ihn

Sato

Fujimoto

et al. 1996

Clinical and Experimental Immunology

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“…It is known that b 2 -GPI binds to negatively charged substances [17][18][19][20] and inhibits the intrinsic blood coagulation pathway [21], adenosine 5Ј-diphosphate (ADP)-dependent aggregation of platelets [22], and prothrombinase activity of platelets [20]. b 2 -GPI is also known as apolipoprotein H, because this protein is collected in lipoprotein fractions of chylomicron, very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), but not in low-density lipoprotein (LDL) [19].…”

Section: Introductionmentioning

confidence: 99%

Involvement of beta2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages

Hasunuma¹,

Matsuura²,

Makita³

et al. 1997

Clin Exp Immunol

229

101

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Anticardiolipin antibodies (aCL) in the sera of patients with antiphospholipid syndrome (APS) recognize an altered structure of beta 2-glycoprotein I (beta 2-GPI) interacting with solid-phase negatively charged phospholipids. beta 2-GPI bound to Cu2+-oxidized plasma lipoproteins, i.e. oxidized very low-density lipoprotein (oxVLDL), oxidized low-density lipoprotein (oxLDL), or oxidized high-density lipoprotein (oxHDL). beta 2-GPI inhibited in vitro uptake, i.e. cell surface binding, cellular association, and proteolytic degradation of oxLDL by murine macrophage J774A.1 cells. The binding of oxLDL to the macrophages was inhibited by the addition of polyinosinic acid (poly (I)), a competitor of the scavenger receptor, but not by another polyanionic acid, polycytidylic acid (poly (C)). Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human beta 2-GPI and monoclonal aCL derived from NZW x BXSB F1 (WB F1) mice, an animal model of APS, or anti-beta 2-GPI antibodies from BALB/c mice immunized with human beta 2-GPI. These findings indicate that beta 2-GPI may be an antiatherogenic protein and that the autoimmune response against beta 2-GPI may have a role in the development of atherosclerosis in APS.

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“…Since b 2 -GPI has strong binding properties to negatively charged proteins or phospholipids involved in coagulation processes, it is likely that aPL may hamper b 2 -GPI-associated coagulation steps. b 2 -GPI inhibits ADP-induced platelet aggregation [17] and factor XII activation [18], therefore the intrinsic clotting pathway [19] and factor Xa generation [20]. Despite these regulatory functions, familial deficiency of b 2 -GPI is not a risk factor for thrombosis [21], and decreased levels are not usually associated with APS [22].…”

Section: Introductionmentioning

confidence: 99%

Binding of anticardiolipin antibodies to protein C via β2-glycoprotein I (β2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system

Atsumi

Khamashta

Amengual

et al. 1998

Clinical and Experimental Immunology

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SUMMARYIt is known that antiphospholipid antibodies (aPL) hamper the anticoagulant activity of the protein C system, but the mechanism is still obscure. In this study, we demonstrate that anticardiolipin antibodies (not anti-protein C autoantibodies) can bind protein C via b 2 -GPI, which bears their binding epitope, in a fashion dependent on negatively charged phospholipids. We studied the binding of IgG from aPL to protein C in the presence of b 2 -GPI by ELISA (anti-'protein C' antibody ELISA), and compared their binding with those obtained in the absence of b 2 -GPI. In the anti-'protein C' antibody ELISA system, 47% of 78 aPL þ patients had a positive titre in the presence of cardiolipin (CL) and b 2 -GPI, but binding was not found in the absence of b 2 -GPI. Highly significant correlations were found between the titre of anti-'protein C' antibody in the presence of b 2 -GPI and that of anti-b 2 -GPI antibody (r ¼ 0·802, P ¼ 0·0001). We further analysed the interaction between protein C, phospholipids, b 2 -GPI and human aCL MoAbs established from patients with antiphospholipid syndrome. In a first set of experiments, the binding of b 2 -GPI to protein C and its phospholipid dependency were investigated. b 2 -GPI bound to protein C in the presence of CL or phosphatidylserine, but not in the presence of phosphatidylcholine or phosphatidylethanolamine. In a second group of experiments, the binding of three human monoclonal aCL recognizing the cryptic epitope of b 2 -GPI (virtually anti-b 2 -GPI antibodies) was evaluated in the presence of cardiolipin and b 2 -GPI. All three human monoclonal aCL bound to protein C in the presence of CL and b 2 -GPI, whereas they did not in the absence of either b 2 -GPI or CL. These data suggest that protein C could be a target of aCL by making a complex with CL and b 2 -GPI, leading to protein C dysfunction.

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

Cited by 333 publications

References 30 publications

Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β2-GPI) in systemic sclerosis

Measurement of anticardiolipin antibodies by ELISA using β2-glycoprotein I (β2-GPI) in systemic sclerosis

Involvement of beta2-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages

Binding of anticardiolipin antibodies to protein C via β2-glycoprotein I (β2-GPI): a possible mechanism in the inhibitory effect of antiphospholipid antibodies on the protein C system

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