Platelet activation by dimeric β2‐glycoprotein I requires signaling via both glycoprotein Ibα and apolipoprotein E receptor 2′

Urbanus, Rolf T.; Pennings, Maarten; Derksen, R. H. W. M.; Groot, Philip G. de

doi:10.1111/j.1538-7836.2008.03021.x

Cited by 117 publications

(111 citation statements)

References 34 publications

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“…The interaction of dimerized β2GP1 with either ApoER2' or GPIbα was found to lower the threshold of platelet activation by collagen or fibronectin surfaces [31,65]. While EC and monocytes do not express ApoER2', other members of LDL-receptor family were shown to bind the dimerized form of β2GP1 [64,66].…”

Section: Apoer2'and Gpibα As Apla Receptorsmentioning

confidence: 99%

Receptors involved in cell activation by antiphospholipid antibodies

Brandt

Kruithof

Moerloose

2013

Thrombosis Research

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The antiphospholipid syndrome (APS) is an autoimmune disease associated with arterial or venous thrombosis and/or recurrent fetal loss and is caused by pathogenic antiphospholipid antibodies (aPLA). The plasma protein β2-glycoprotein 1 (β2GP1) has been identified as a major target of aPLA associated with APS. Cell activation by aPLA appears to be a major pathogenic cause in the pathogenesis of APS. Receptors, co-receptors and accessory molecules are known to assist the pathogenic effects of aPLA. Members of the TLR family and the platelet receptor apolipoprotein E receptor 2' (apoER2'), a receptor belonging to the low-density lipoprotein receptor (LDL-R) family, as well as GPIbα, were identified as putative candidates for aPLA recognition. CD14, a co-receptor for TLR2 and TLR4, and annexin A2, a ubiquitous Ca2+ -binding protein that is essential for actin-dependent vesicle transport, could serve as important accessory molecules in mediating the pathogenic effects of aPLA. Finally, complement activation has been reported in association with the pathogenicity of APS. The relative contribution of these different mechanisms in the pathogenesis of APS is controversial. Here, we review the various in vivo and in vitro models that have been used to investigate the pathogenic mechanisms of aPLA in APS

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Section: Apoer2'and Gpibα As Apla Receptorsmentioning

confidence: 99%

Receptors involved in cell activation by antiphospholipid antibodies

Brandt

Kruithof

Moerloose

2013

Thrombosis Research

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“…This has led to the development of an artificial dimer of LA1 of LRP8, which effectively inhibits the binding of ␤ 2 GPI-antibody complexes to phospholipid surfaces. 111 The efficacy of soluble LA1 of LRP8 as an inhibitor of the prothrombotic effects of antiphospholipid antibodies has been shown extensively both in vitro 77,90,112 and in vivo. 76 However, LDL-receptor family members are ubiquitous and are involved in several important processes, including protein clearance, lipoprotein metabolism and neuronal plasticity.…”

Section: Attenuation Of the Activity Of The Autoantibodiesmentioning

confidence: 99%

The significance of autoantibodies against β2-glycoprotein I

Groot

Urbanus

2012

Blood

132

115

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AbstractThe antiphospholipid syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with a history of thrombosis and/or pregnancy morbidity, including fetal loss. APS is an autoimmune disease with a confusing name because the pathologic auto-antibodies are shown to be directed against the plasma protein β2-glycoprotein I and not against phospholipids. In fact, auto-antibodies that recognize phospholipids themselves are not associated with thrombosis but with infectious diseases. One of the intriguing questions is why autoantibodies against β2-glycoprotein I are so commonly found in both patients and the healthy. Several potential mechanisms have been suggested to explain the increased thrombotic risk in patients with these autoantibodies. In this overview, we will summarize our knowledge on the etiology of the autoantibodies, and we will discuss the evidence that identify autoantibodies against β2-glycoprotein I as the culprit of APS.

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“…Additionally, a recombinant-binding domain I of ApoER2 has been shown to act as an inhibitor of increased thrombus formation in different murine models of APS. Moreover, aPL-induced increases in leucocyte adhesion to endothelium, peritoneal macrophage TF activity/expression and thrombus formation were significantly reduced in ApoER2 (À/À) mice (Urbanus et al, 2008b;Romay-Penabad et al, 2011). Interestingly, ApoER2′ needs a receptor cooperation for its optimal function and specificity.…”

Section: Open Questionsmentioning

confidence: 99%

The role of TLR4 in pathophysiology of antiphospholipid syndrome‐associated thrombosis and pregnancy morbidity

et al. 2013

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SummaryThe antiphospholipid syndrome (APS) is an autoimmune disease characterized by the clinical features of recurrent thrombosis in the venous or arterial circulation and fetal losses. Antiphospholipid antibodies (aPL), particularly against the phospholipid binding protein beta-2 glycoprotein I (b2GPI), play an important role in APS pathological mechanisms. aPL can activate intracellular signal transduction in a b2GPI-dependent manner to induce inflammatory responses, and promote hypercoagulable state and recurrent spontaneous abortion when b2GPI is associated with the cell surface receptor. In vivo and in vitro studies show that Annexin A2 (ANXA2) is the high affinity receptor that connects b2GPI to the target cells. However, ANXA2 is not a transmembrane protein and lacks an intracellular signal transduction pathway. Growing evidences suggest that the transmembrane protein toll-like receptor 4 (TLR4) might act as an 'adaptor' for intracellular signal transduction. This review focuses on the role of TLR4 and its signalling pathway in APS pathological mechanisms which will help us better understand the pathological processes of this syndrome.

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Platelet activation by dimeric β2‐glycoprotein I requires signaling via both glycoprotein Ibα and apolipoprotein E receptor 2′

Abstract: To cite this article: Urbanus RT, Pennings MTT, Derksen RHWM, de Groot PG. Platelet activation by dimeric b 2 -glycoprotein I requires signaling via both glycoprotein Iba and apolipoprotein E receptor 2¢.

Cited by 117 publications

References 34 publications

Receptors involved in cell activation by antiphospholipid antibodies

Receptors involved in cell activation by antiphospholipid antibodies

The significance of autoantibodies against β2-glycoprotein I

The role of TLR4 in pathophysiology of antiphospholipid syndrome‐associated thrombosis and pregnancy morbidity

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