Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02749 (beta2-glycoprotein I)
 836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present paper the influence of beta 2-glycoprotein-I, also known as apolipoprotein H, upon the prothrombinase activity of platelets and phospholipid vesicles was investigated. The results can be summarized as follows. 1. The prothrombinase activity of resting, non-activated platelets, lysed platelets and vesicles composed of phosphatidylserine and phosphatidylcholine at different molar ratios is inhibited by beta 2-glycoprotein-I in a dose-dependent manner. The concentration of glycoprotein which produces marked inhibition is within the physiological plasma concentration range of beta 2-glycoprotein-I. 2. The time dependence of this inhibition is a relatively slow process, which is not fully expressed before 1 h of incubation. 3. The effect of the glycoprotein is not due to a direct interaction with the components of the prothrombinase complex, i.e. factors Xa, Va, Ca2+ or prothrombin, nor is the inhibitory action abolished by increasing concentrations of coagulation factors Xa and Va. This suggests that beta 2-glycoprotein-I causes a reduction of the prothrombinase binding sites of these coagulation factors to platelets or phospholipid vesicles. 4. The prothrombinase activity of platelets stimulated with ionophore A23187 or with collagen plus thrombin is also inhibited by beta 2-glycoprotein-I in a manner similar to that observed for phospholipid vesicles or for lysed platelets. These findings suggest a regulatory role for beta 2-glycoprotein-I in the pathway of blood coagulation.
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PMID:Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I. 376 9

We studied sera from patients with various disorders including collagen diseases, Buerger's disease, deep vein thrombosis, repeated abortions and idiopathic thrombocytopenic purpura in order to measure anticardiolipin antibody (aCL) titers. In our assay system, we can detect aCL against bovine cardiolipin and the complex of cardiolipin and beta 2-glycoprotein I (beta 2-GPI). This was done with simultaneous assays using blank wells and bovine cardiolipin coated wells in the EIA method in which both wells were also coated with bovine serum albumin possibly containing beta 2-GPI, then aCL titers was given by subtraction of O.D. values of blank wells from those of cardiolipin coated wells. When the aCL was quantified by anti human immunoglobulin antibodies, collagen diseases showed positive aCL in 15 (11.5%) out of 130 sera with positive anti ENA antibodies, 3 (11.1%) out of 27 sera with positive anti DNA antibodies and 3 (5.2%) out of 58 sera with other positive ANA sera. The other hand, we found positive aCL in 2 (4.9%) out of 41 sera from patients with Buerger's disease, 4 (36.4%) out of 11 sera from patients with deep vein thrombosis, 1 (7.7%) out of 13 sera from patients with repeated abortions and 6 (14.6%) out of 41 sera from patients with idiopathic thrombocytopenic purpura. Twenty one (61.8%) out of these aCL positive sera had also positive IgG-aCL for the assay using anti human IgG antibody. Compared to previous reports, we thought, low incidence of aCL in our study was due to exclusion of anti beta 2-GPI antibody in our assay system.
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PMID:[Detection of anticardiolipin antibody using the EIA kit prepared to eliminate interference of serum cofactor]. 837 6

We investigated the role of alpha IIb beta 3 in microparticle generation by normal and thrombasthenic platelets stimulated with collagen plus thrombin. Microparticle generation by normal platelets was scarcely inhibited by monoclonal antibodies for glycoprotein Ib and glycoprotein IX. Although one monoclonal anti-alpha IIb beta 3 antibody (NNKY1-32) partly inhibited microparticle generation, 3 other monoclonal anti-alpha IIb beta 3 antibodies had little effect. However, the combination of 4 monoclonal anti-alpha IIb beta 3 antibodies or treatment with a polyclonal anti-alpha IIb beta 3 antibody significantly inhibited microparticle generation (p < 0.05). Microparticle generation by thrombasthenic platelets also occurred after stimulation with collagen plus thrombin, although at a significantly lower level compared with normal platelets. Monoclonal antibodies for resting alpha IIb beta 3, P-selectin, activated alpha IIb beta 3 and beta 2-glycoprotein I bound to microparticles from healthy platelets. In contrast, only a monoclonal antibody for beta2-glycoprotein I bound to thrombasthenic microparticles. These results suggest that microparticle generation by collagen plus thrombin occurs via two different mechanisms which are dependent and independent of alpha IIb beta 3, respectively. The alpha IIb beta 3-dependent mechanism appears to require activation of alpha IIb beta 3.
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PMID:Participation of alpha IIb beta 3 in platelet microparticle generation by collagen plus thrombin. 869 76

We measured serum antiphospholipid antibodies (aPL) in patients with multiple sclerosis (MS) using enzyme linked immunosorbent assay (ELISA) and examined the correlations between these antibodies and MS. This study included thirty-two patients with clinically definite MS, thirteen patients with other autoimmune neurological diseases excluding collagen diseases (disease control A), eight patients with collagen vascular diseases (disease control B) and twenty-six healthy persons (normal control). In MS group IgG antibody against cardiolipin (CL) was detected in 3 (9%); among them, cofactor (beta 2-glycoprotein I) dependency was shown in 2 but one was cofactor independent. IgM antibody was elevated in 14 of 32 patients (44%) with MS, but cofactor dependency was not determined. However, this was significantly higher in frequency than that of the disease control A (p < 0.01) and normal control (p < 0.01). Results of antibodies against phosphatidylserine were found similar to CL, but antibodies against phosphatidylcholine were in most cases negative. Each of anti-CL IgG antibody purified from four patients with diverse immunological disorders (primary antiphospholipid antibody syndrome, MS, polyarteritis nodosa and systemic lupus erythematosus) had different reactivities against DNA. In addition, the aPL positive group in MS possessed the autoantibodies such as antinuclear antibody at higher rate than the negative group. However, clinically two groups of MS were indistinguishable. The higher incidence of aPL may imply that a broad spectrum of autoantibodies might be produced in MS; some antibodies presumably related directly to MS pathogenesis are yet to be identified.
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PMID:Characterization of serum anti-phospholipid antibodies in patients with multiple sclerosis. 872 2

We report two cases of antiphospholipid antibody syndrome with elevated anti-beta 2-glycoprotein I antibodies. Patient 1 had systemic lupus erythematosus (SLE) and was treated with an oral corticosteroid and aspirin. There were foci of sheathed retinal arterioles appearing as white lines in the fundus of both eyes. The sheathed arterioles of the peripheral fundus of the right eye were completely or incompletely occluded. Recanalization occurred during a 10 month follow-up. Patient 2 had hypertension and multiple brain infarction but no association with collagen diseases. Major retinal arterioles showed sheathing. Fluorescein angiography demonstrated progressive occlusion or stenosis of these major arterioles with extensive insufficiency of regional capillary bed circulation. Retinal photocoagulation was applied to both eyes which developed neovascularization. Vitrectomy was performed in the left eye with recurrent vitreous hemorrhage. Antiphospholipid antibody syndrome should be considered in cases of sheathed or white retinal arterioles.
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PMID:[The time course of white retinal arterioles in two cases of antiphospholipid antibody syndrome]. 972 Mar 68

We report a case of acute adrenal insufficiency in a context of probable bilateral adrenal haemorrhage, as revealed by CT-scan in a 52-year-old woman with a history of spontaneous abortion and repeated ischaemic stroke without symptoms or signs of collagen vascular disease. The symptoms began after the patient had successfully been treated for pneumonia. She had persistently high titres of IgG anticardiolipin antibodies, antibodies against beta 2-glycoprotein I and a lupus anticoagulant. The diagnosis of primary antiphospholipid syndrome with adrenal insufficiency was postulated.
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PMID:[Bilateral adrenal hemorrhage with adrenal insufficiency in the framework of primary antiphospholipid antibody syndrome]. 1082

Patients with prolonged clotting times caused by lupus anticoagulant (LAC) are at risk for thrombosis. This paradoxal association is not understood. LAC is frequently caused by anti-beta2-glycoprotein I (beta 2GPI) antibodies. Antibody-induced dimerization of beta 2GPI increases the affinity of beta 2GPI for phospholipids, explaining the observed prolonged clotting times. We constructed dimers of beta 2GPI that mimic effects of beta 2GPI-anti-beta 2GPI antibody complexes, and we studied their effects on platelet adhesion and thrombus formation in a flow system. Dimeric beta 2GPI increased platelet adhesion to collagen by 150% and increased the number of large aggregates. We also observed increased platelet adhesion to collagen when whole blood was spiked with patient-derived polyclonal anti-beta 2GPI or some, but not all, monoclonal anti-beta 2GPI antibodies with LAC activity. These effects could be abrogated by inhibition of thromboxane synthesis. A LAC-positive monoclonal anti-beta 2GPI antibody, which did not affect platelet adhesion, prevented the induced increase in platelet adhesion by beta 2GPI dimers. Furthermore, increased platelet adhesion disappeared after preincubation with receptor-associated protein, a universal inhibitor of interaction of ligands with members of the low density lipoprotein receptor family. Using co-immunoprecipitation, it was shown that dimeric beta 2GPI can interact with apolipoprotein E receptor 2 (apoER2'), a member of the low density lipoprotein receptor family present on platelets. These results demonstrate that dimeric beta 2GPI induces increased platelet adhesion and thrombus formation, which depends on activation via apoER2'.
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PMID:Dimers of beta 2-glycoprotein I increase platelet deposition to collagen via interaction with phospholipids and the apolipoprotein E receptor 2'. 1280 92

Among the heterogeneous antiphospholipid antibodies, many studies suggest that those directed to beta2-glycoprotein I (beta2GPI) are the major pathogenic antibodies in antiphospholipid syndrome (APS). They have been shown to activate the coagulation pathway via several mechanisms, activate platelets via thrombin formation, and suppress fibrinolysis. Additionally, we propose another possible mechanism that involves certain chemokines and results in platelet activation. This hypothesis is based on the observations that anti-beta2GPI antibodies stimulated monocytes to secrete inflammatory cytokines such as IL-1beta and TNF-alpha, which in turn stimulated vascular endothelial cells to express chemokines such as CX3CL1 and CCL5. CX3CL1 increased the ability of normal platelets to adhere to collagen at a high shear rate, while CCL5 induced platelet aggregation. Expression of tissue factor, IL-1beta, and TNF-alpha by monocytes stimulated with anti-beta2GPI antibodies, as well as CX3CL1 and CCL5 by vascular endothelial cells stimulated with IL-1beta or TNF-alpha were all suppressed by the NF-kappaB-specific inhibitor DHMEQ. These results suggest that the NF-kappaB pathway may be a potential therapeutic target relating to both the coagulation pathway and platelet activity.
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PMID:Possible involvement of chemokine-induced platelet activation in thrombophilic diathesis of antiphospholipid syndrome. 1975 42