Prothrombinase activity of human platelets is inhibited by β2-glycoprotein-I

Nimpf, Johannes; Bevers, Edouard M.; Bomans, Paul H. H.; Till, U; Wurm, H.; Kostner, Gerhard M.; Zwaal, R.F.A.

doi:10.1016/0304-4165(86)90237-0

Cited by 323 publications

(161 citation statements)

References 20 publications

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“…Beta,-glycoprotein I is a cationic protein that is able to play a natural anticoagulant role by binding to anionic procoagulant surfaces, including membranes of cells involved in the coagulation cascade (23)(24)(25)(26). In view of this, &GPI binding to human EC membranes has recently been reported in both in vitro and ex vivo studies (27)(28)(29).…”

mentioning

confidence: 99%

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

Papa

Guidali

Sala

et al. 1997

Arthritis & Rheumatism

270

142

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Objective. To investigate the ability of human anti-&-glycoprotein I (anti-&GPI) antibodies to recognize the cofactor adherent on endothelial cells (EC) and to modulate endothelial functions.Methods. Six human affinity-purified polyclonal anti-P,GPI IgG and 2 IgM monoclonal antibodies (MAb) were obtained from patients with the antiphospholipid syndrome. The antibodies were tested for their ability to 1) bind to endothelial monolayers through the adherent f3,GPI and 2) modulate endothelial adhesion molecule expression and interleukin-6 (IL-6) and 6-keto-prostaglandin F,, (6-keto-PGF1,) secretion.Results. The affinity-purified IgG and the MAb with anti-&GPI activity, but not the respective controls, displayed EC binding, which declined on cells incubated in serum-free medium and was restored in a dose-dependent manner by exogenous human P,GPI. After EC binding, both polycJonaJ and monoclonal antibodies up-regulated adhesion molecule expres-

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mentioning

confidence: 99%

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

Papa

Guidali

Sala

et al. 1997

Arthritis & Rheumatism

270

142

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“…β2GPI, also known as apolipoprotein H, is a 50-kDa phospholipid-binding protein present in plasma at an approximate concentration of 200µg/ml, and has been recognized as a natural anti-coagulant because β2GPI inhibits prothrombinase and tenase function, factor XII activation and ADP-dependent activation of platelets (Nimpf et al, 1986;Schousboe et al, 1995;Nimpf et al, 1985). Recently, β2GPI has been shown to bind directly to factor XI and attenuate its activation (Shi et al, 2004).…”

Section: Impaired Fibrinolysismentioning

confidence: 99%

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway

et al. 2005

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Antiphospholipid syndrome (APS) is characterized by recurrent thrombosis or pregnancy morbidity associated with antiphospholipid antibodies (aPL). Impaired fibrinolysis is a contributing factor for the development of thrombosis, and the effect of aPL in the fibrinolytic system has been investigated. Impaired release of tPA and enhanced release of PAI-1 after endothel activation is reported in patients with APS. Elevated Lipoprotein (a) levels have been found in APS, which results in inhibition of fibrinolytic activity. Phospholipid-bound β 2 -glycoprotein I (β 2 GPI) is a major autoantigen for aPLs. β2GPI exerts both anti-coagulant and pro-coagulant properties mainly by interacting with other phospholipid-binding proteins such as coagulation factors and protein C. Dramatic increase in the affinity of β 2 GPI to the cell surface is induced by binding of pathogenic anti-β 2 GPI antibodies, which may modify the physiological function of β 2 GPI and may affect the coagulation/fibrinolysis balance on the cell surface.Using chromogenic assays for measuring fibrinolytic activity, we demonstrated that addition of monoclonal anticardiolipin antibody (aCL) decreases the activity of extrinsic/intrinsic fibrinolysis. Significantly lower activity of intrinsic fibrinolysis was also demonstrated in the euglobulin fractions from APS patients.Endothelial cells and monocytes are activated by aPLs in vitro, resulting in production of tissue factor (TF), a major initiator of the coagulation system. Recently, aPLs are reported to induce thrombocytes to produce thromboxane. The importance of apoE receptor 2 on platelets for the binding of artificially-dimerized β 2 GPI was suggested. By investigating aPL-inducible genes in peripheral blood mononuclear cells, we found that mitogen-activated protein kinase (MAPK) pathway was up-regulated. Using monocyte cell line, phosphorylation of p38 MAPK, NF-κB 3 translocation to the nuclear fraction, and up-regulated TF mRNA expression were demonstrated after treatment with monoclonal aCL. These phenomena were observed only in the presence of β 2 GPI. Moreover, a specific p38 MAPK inihibitor SB203580 decreased aCL/β 2 GPI-induced TF mRNA expression.

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“…In vitro, ␤ 2 GPI binds to negatively charged phospholipids (such as cardiolipin [CL] and phosphatidylserine [PS]) as well as inhibiting contact activation of the intrinsic coagulation pathway (33), platelet prothrombinase activity (34), and ADPmediated platelet aggregation (35). It also aids clearance of oxidized low-density lipoproteins (LDL) (36).…”

Section: Molecular Structure and Function Of ␤ 2 Gpimentioning

confidence: 99%

How do antiphospholipid antibodies bind β₂‐glycoprotein I?

Giles¹,

Isenberg²,

Latchman³

et al. 2003

Arthritis & Rheumatism

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Prothrombinase activity of human platelets is inhibited by β2-glycoprotein-I

Cited by 323 publications

References 20 publications

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway

How do antiphospholipid antibodies bind β₂‐glycoprotein I?

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Prothrombinase activity of human platelets is inhibited by β2-glycoprotein-I

Cited by 323 publications

References 20 publications

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β2‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2‐Glycoprotein I and Induce Endothelial Activation

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β2‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β2‐Glycoprotein I and Induce Endothelial Activation

Pathogenesis of antiphospholipid antibodies: impairment of fibrinolysis and monocyte activation via the p38 mitogen-activated protein kinase pathway

How do antiphospholipid antibodies bind β2‐glycoprotein I?

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Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

Endothelial cells as target for antiphospholipid antibodies. Human Polyclonal and Monoclonal Anti‐β₂‐Glycoprotein I Antibodies React In Vitro with Endothelial Cells Through Adherent β₂‐Glycoprotein I and Induce Endothelial Activation

How do antiphospholipid antibodies bind β₂‐glycoprotein I?