β2-glycoprotein-I (apolipoprotein H) interactions with phospholipid vesicles

Wurm, H.

doi:10.1016/0020-711x(84)90168-x

Cited by 242 publications

(164 citation statements)

References 18 publications

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“…Role of ␤ 2 GPI in Phagocytosis-Because ␤ 2 GPI binds PScontaining vesicles in vitro (21,26) and in vivo (13) and influences their clearance from the peripheral circulation (13), it seems reasonable to assume that this protein might serve as a specific marker for the recognition of PS-expressing cells. To model PS-dependent phagocytosis, the influence of ␤ 2 GPI on the uptake of PS-containing liposomes and PS-expressing lipid FIG.…”

Section: Resultsmentioning

confidence: 99%

“…Carrier-free 125 Ilabeled PE was synthesized as described previously (19). ␤ 2 GPI was purified from pooled human plasma (Gulf Coast Regional Blood Center, Houston, TX) by perchloric acid precipitation, ion exchange chromatograhy, and heparin affinity chromatography as described previously (20,21). Human serum albumin (25% USP) was from Alpha Therapeutics (Los Angeles, CA).…”

Section: Methodsmentioning

confidence: 99%

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Immune Clearance of Phosphatidylserine-expressing Cells by Phagocytes

Balasubramanian

Chandra

Schroit

1997

Journal of Biological Chemistry

144

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The function of ␤ 2 -glycoprotein I (␤ 2 GPI), a 50-kDa serum glycoprotein, is not completely understood but has been suggested to be involved in the regulation of thrombosis ( To further understand the role of this protein, we characterized the ability of ␤ 2 GPI to interact with PS vesicles and influence their uptake by macrophages in vitro. ␤ 2 GPI bound to and precipitated vesicles containing anionic but not zwitterionic phospholipids in a gel diffusion assay. ␤ 2 GPI also inhibited the procoagulant activity of PS liposomes. In vitro phagocytosis studies showed 20-fold greater uptake of PS liposomes over phosphatidylcholine liposomes. This enhanced uptake was maintained even after PS was "shielded" with ␤ 2 GPI and further increased upon the addition of ␤ 2 GPI antibodies. Similar to liposomes, PS-expressing apoptotic thymocytes and lipid symmetric red blood cell ghosts bound ␤ 2 GPI. Macrophage uptake of these cells was also maintained or enhanced in the presence of ␤ 2 GPI and further increased upon the addition of ␤ 2 GPI antibodies. It is concluded that ␤ 2 GPI can play a critical role in hemostasis by influencing both thrombosis and the clearance of PS-expressing cells.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Immune Clearance of Phosphatidylserine-expressing Cells by Phagocytes

Balasubramanian

Chandra

Schroit

1997

Journal of Biological Chemistry

144

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“…19 ␤ 2 -Glycoprotein I is a plasma protein that binds negatively charged surfaces, including anionic phospholipid vesicles and platelets, and this interaction inhibits platelet-and phospholipid-dependent coagulation reactions. 18,20 Furthermore, Chonn et al 12 identified ␤ 2 -glycoprotein I as a major protein that binds to liposomes with a short half-life in vivo and noted that pretreating mice with anti-␤ 2 -glycoprotein I antibodies markedly increased the circulating half-life of the liposomes. In vitro, ␤ 2 -glycoprotein I promotes the uptake of anionic phospholipid vesicles and platelet-derived microvesicles by macrophages.…”

Section: Discussionmentioning

confidence: 99%

Sulfatides

et al. 2003

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Background-Sulfatides are sulfated glycosphingolipids expressed on the surface of erythrocytes, leukocytes, and platelets. Sulfatides interact with several cell adhesion molecules involved in hemostasis. ␤ 2 -Glycoprotein I is an anionic phospholipid-binding plasma protein, and the phospholipid-bound form is the target for most anti-phospholipid antibodies that are associated with recurrent thrombosis, miscarriages, and neurological symptoms. In this study, we examined whether ␤ 2 -glycoprotein I forms a complex with sulfatides and thereby becomes a target for anti-phospholipid antibodies. Methods and Results-␤ 2 -Glycoprotein I binds to surface-bound sulfatides but not to other glycolipids, such as ceramide, cerebrosides, sphingomyelin, or ganglioside. At a sulfatide coating density of 1 g/well, ␤ 2 -glycoprotein I reaches half-maximal binding at 2.5 g/mL, and the binding is saturated at 10 g/mL. The binding of ␤ 2 -glycoprotein I also depends on the coating density of sulfatides in the well. At a constant ␤ 2 -glycoprotein I concentration of 5 g/mL, maximal binding of ␤ 2 -glycoprotein I is observed at a coating density of 1 g/well. The serum from 14 patients with anti-cardiolipin antibodies, a subset of anti-phospholipid antibodies, bound to sulfatide-bound ␤ 2 -glycoprotein I and previous absorption on cardiolipin-coated surfaces decreased the immunoreactivity toward sulfatide-␤ 2 -glycoprotein I complex by Ͼ50% in 12 of 14 patients. Furthermore, immunoaffinity-purified anti-cardiolipin antibodies from 4 of 5 patients reacted with sulfatide-bound ␤ 2 -glycoprotein I. Conclusions-These results show that not only anionic phospholipids, as commonly known, but also sulfatides are targets for most anti-phospholipid antibodies. We therefore postulate that interactions of these antibodies with sulfatides may contribute to some of the clinical symptoms of the anti-phospholipid antibody syndrome.

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“…A member of the shortconsensus repeat protein family, beta2-GPI is characterized by five 'sushi-domains'. The fifth sushi-domain contains the binding site to phospholipid, and it attaches to activated cellular surfaces [31]. β2-GPI binds to various negatively charged phospholipids and inhibits intrinsic blood coagulation pathway [32], prothrombinase activity of human platelets [33] , and adenosine diphosphate (ADP) dependent platelet aggregation [34].…”

Section: Genes Associated With Antiphospholipid Syndromementioning

confidence: 99%

Genetics of Antiphospholipid Syndrome

Hancer¹

2011

Human Genet Embryol

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Antiphospholipid syndrome (APS) is defined as recurrent arterial and/or venous thrombosis and obstetric complications in the presence of antiphospholipid antibodies (aPL). The possibility of a genetic predisposition to develop antiphospholipid syndrome (APS) and to produce anticardiolipin antibodies and lupus anticoagulant has been examined by family studies and population studies. Similar to many other polygenic autoimmune diseases, human leukocyte antigen associations have been reported. The genetics of β2-glycoprotein I, one of the most representative target antigens of aPL, has been extensively studied. Additional genetic risk factors for the development of thrombosis in patients with aPL have also been discussed. Although the mechanisms and pathophysiology of thrombosis in APS are highly heterogeneous and multifactorial, different genes seem to be involved.The term "antiphospholipid syndrome" has been proposed to describe the association of arterial and venous thrombosis, recurrent fetal loss, and immune thrombocytopenia with a spectrum of autoantibodies directed against cellular phospholipid components. Because of the antigen spesifity of antiphospholipid antibodies (aPL) and the pathophysiology of thrombosis in antiphospholipid syndrome (APS) are heterogeneous and multifactorial, a single scenario can not explain the mechanisms of thrombophilia or pregnancy morbidity in pateints. Investigation of the clinical epidemiology of APS is in its early stages. During the past 20 years, studies of aPL and APS have been made in many countries [1][2][3][4][5][6][7][8][9][10][11]. aPL appear to occur in all populations studied, with some variations noted in their frequency and in the clinical complications [1,9,10,12,13]. Environmental and genetic factors contribute to ethnic variation and susceptibility to APS and thus interethnic differences in disease patterns may be due to environmental or genetic factors, or both [1,14]. A genetic basis for aPL antibodies was suggested for the first time when a familial clustering of chronic false-positive syphilis test individuals were detected [15]. The first description about aPL showed two pairs of siblings with lupus anticoagulant (LA) [16]. Subsequently, primary APS was described [17] and Cevallos et al. [18] reported the development of primary APS in one woman whose identical twin sister was an asymptomatic carrier of aPL. Relatives of patients with sistemic lupus erythematosus (SLE) or primary APS had a higher incidence of anticardiolipin antibodies (aCL) [19,20] suggesting that a genetic factor may relevant with aPL. Mackie et al. [21] reported three families having more than one member with LA and called familial lupus anticoagulants. The identification of several pedigrees with an increased frequency of aPL antibodies and the associated clinical manifestations further support the familial form of APS. In one of these studies, a large kindred in which nine individuals had aPL antibodies was described. Associated clinical manifestations included stroke, deep ve...

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β2-glycoprotein-I (apolipoprotein H) interactions with phospholipid vesicles

Cited by 242 publications

References 18 publications

Immune Clearance of Phosphatidylserine-expressing Cells by Phagocytes

Immune Clearance of Phosphatidylserine-expressing Cells by Phagocytes

Sulfatides

Genetics of Antiphospholipid Syndrome

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