Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antiphospholipid-protein antibodies (APA) are a family of immunoglobulins which recognize protein-phospholipid complexes. Among the proteins implicated are: beta 2 Glycoprotein I, prothrombin, Annexin V, protein C, and protein S. Laboratory tests are used to identify, predict potential clinical complications, and manage patients with the antiphospholipid-protein syndrome (APS). Emerging evidence suggests laboratory tests can be used to stratify relative risk of patients with APA.
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PMID:Antiphospholipid-protein antibodies: clinical use of laboratory test results (identification, predictive value, treatment). 897 40

"Antiphospholipid" antibodies (aPL) are a heterogenous group of autoantibodies with clinical importance because of their association with thrombotic events, both venous and arterial. Traditionally, aPL have been assayed using phospholipid-dependent tests and are classified as lupus anticoagulants and anticardiolipin antibodies (ACA), based on the method of detection. Most antibodies associated with the aPL syndrome and detected in standard assays are actually directed against two phospholipid-binding plasma proteins, beta 2 glycoprotein I and prothrombin. These antibodies can also be detected in immunoassays (ELISA) utilizing purified protein antigens, in the absence of phospholipids. The main advantage of beta 2 GPI-ELISA compared with conventional cardiolipin-ELISA appearing from initial clinical studies is greater specificity for the aPL syndrome, due to (i) ignorance of "authentic" ACA that interact directly with cardiolipin; (ii) detection of species specific anti-beta 2 GPI antibodies poorly reactive with bovine beta 2 GPI in the cardiolipin-ELISA. Other proteins proposed as target antigens of aPL are protein C, protein S, annexin V, high- and low-molecular weight kininogens, the latter being involved in the binding of antibodies to phosphatidylethanolamine. The possibility that particular autoantibodies (or combinations of autoantibodies) explain the observed clinical spectrum of the aPL syndrome is attractive, but much remains to be learned about their pathogenicity and origin in order to improve diagnosis and therapy.
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PMID:[New targets of antiphospholipid antibodies]. 916 56

Blocking protein C binding to the endothelial cell protein C receptor (EPCR) on the endothelium is known to reduce protein C activation rates. Now we isolate human EPCR and thrombomodulin (TM) and reconstitute them into phosphatidylcholine vesicles. The EPCR increases protein C activation rates in a concentration-dependent fashion that does not saturate at 14 EPCR molecules/TM. Without EPCR, the protein C concentration dependence fits a single class of sites (Km = 2.17 +/- 0.13 microM). With EPCR, two classes of sites are apparent (Km = 20 +/- 15 nM and Km = 3.2 +/- 1.7 microM). Increasing the EPCR concentration at a constant TM concentration increases the percentage of high affinity sites. Holding the TM:EPCR ratio constant while decreasing the density of these proteins results in a decrease in the EPCR enhancement of protein C activation, suggesting that there is little affinity of the EPCR for TM. Negatively charged phospholipids also enhance protein C activation. EPCR acceleration of protein C activation is blocked by anti-EPCR antibodies, but not by annexin V, whereas the reverse is true with negatively charged phospholipids. Human umbilical cord endothelium expresses approximately 7 times more EPCR than TM. Anti-EPCR antibody reduces protein C activation rates 7-fold over these cells, whereas annexin V is ineffective, indicating that EPCR rather than negatively charged phospholipid provide the surface for protein C activation. EPCR expression varies dramatically among vascular beds. The present results indicate that the EPCR concentration will determine the effectiveness of the protein C activation complex.
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PMID:Reconstitution of the human endothelial cell protein C receptor with thrombomodulin in phosphatidylcholine vesicles enhances protein C activation. 1003 68

The clinically relevant antiphospholipid antibodies (APA) include anticardiolipin antibodies and lupus anticoagulant. Most autoimmune APA require the presence of a cofactor for phospholipid binding, and the growing list of candidate cofactors has prompted redefinition of APA to 'antiphospholipid protein antibodies'. Current evidence favours beta2-glycoprotein I (beta2GPI) and prothrombin as the primary antigens for anticardiolipin antibodies and lupus anticoagulant respectively. Patients with APA show a predisposition for venous and arterial thromboembolism, recurrent fetal loss, thrombocytopenia and a number of neurological syndromes and miscellaneous conditions. The association between APA and thrombosis has been well documented, but a definite mechanism remains to be clarified. Proposed mechanisms have included disruption of endothelial regulatory processes, impairment of fibrinolysis, augmented platelet activation and/or adhesion, inhibition of antithrombin activity and negation of the anticoagulant effects of beta2GPI and annexin V. In this review we describe recent insights into the role of beta2GPI as a natural anticoagulant, the procoagulant effects of APA on the Protein C system, the interactions between APA and prothrombin resulting in augmentation of thrombin generation, and cellular expression of Tissue Factor in patients with APA. Cellular immunity to beta2GPI is also discussed. Elucidation of these pathophysiological mechanisms may shed further light on the association between APA and thrombosis.
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PMID:Recent insights into antiphospholipid antibody-mediated thrombosis. 1085 78

We have investigated beta2-glycoprotein I (beta2GPI) binding to platelet-derived microparticles (PMP) and its effect on GPIIb/IIIa. PMP were isolated from washed human platelets after stimulation with A23187, and analyzed by surface plasmon resonance spectroscopy. Beta2GPI as well as activated protein C (APC) or annexin V bound to PMP-coated sensorchips, demonstrating exposure of anionic phospholipids on immobilized PMP. Beta2GPI binding was impaired by calcium and occurred in a concentration-dependent manner with apparent k(on) = 2.6 x 10(4) M(-1) s(-1) and k(off) = 4.4 x 10(-3) s(-1), corresponding to a KD value of 1.7 x 10(-7) M. When analyzed by flow cytometry, the binding of certain mAbs specific for GPIIb and/or GPIIIa was reduced in the presence of beta2GPI but not of APC or annexin V, whereas the binding of anti-GPIb or anti-P-selectin mAbs, or of soluble fibrinogen remained unchanged. These results suggest a broad but specific influence of beta2GPI on GPIIb/IIIa immunoreactivity, and indicate that beta2GPI may act as a modulator of GPIIb/IIIa-dependent functions of PMP.
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PMID:Beta2-glycoprotein I binding to platelet microparticle membrane specifically reduces immunoreactivity of glycoproteins IIb/IIIa. 1124 54

We determined the numbers, cellular origin and thrombin-generating properties of microparticles in healthy individuals (n = 15). Microparticles, isolated from fresh blood samples and identified by flow cytometry, originated from platelets [237 x 10(6)/L (median; range 116-565)], erythrocytes (28 x 10(6)/L; 13-46), granulocytes (46 x 10(6)/L; 16-94) and endothelial cells (64 x 10(6)/L; 16-136). They bound annexin V, indicating surface exposure of phosphatidylserine, and supported coagulation in vitro. Interestingly, coagulation occurred via tissue factor (TF)-independent pathways, because antibodies against TF or factor (F)VII were ineffective. In contrast, in our in vitro experiments coagulation was partially inhibited by antibodies against FXII (12%, p = 0.006), FXI (36%, p <0.001), FIX (28%, p <0.001) or FVIII (32%, p <0.001). Both the number of annexin V-positive microparticles present in plasma and the thrombin-generating capacity inversely correlated to the plasma concentrations of thrombin-antithrombin complex (r = -0.49, p = 0.072 and r = -0.77, p = 0.001, respectively), but did not correlate to prothrombin fragment F1+2 (r = -0.002, p = 0.99). The inverse correlations between the number of microparticles and their thrombin-forming capacity and the levels of thrombin-antithrombin complex in plasma may indicate that microparticles present in the circulation of healthy individuals have an anticoagulant function by promoting the generation of low amounts of thrombin that activate protein C. We conclude that microparticles in blood from healthy individuals support thrombin generation via TF- and FVII-independent pathways, and which may have an anticoagulant function.
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PMID:Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. 1134 98

Antiphospholipid antibodies(APA) have been reported to be a heterogeneous family of immunoglobulins. Some APA can be detected via phospholipid dependent coagulation assays when they present as an aspecific coagulation inhibitor, lupus anticoagulant(LA), other antibodies can be measured via immunological assays mostly via their capability to bind to immobilized cardiolipin (anticardiolipin antibody; aCL). Despite their name, APA associated with antiphospholipid syndrome(APS) do not bind phospholipids, but are directed at plasma proteins bound with anionic phospholipids. The antigenic targets of these antibodies include beta 2 glycoprotein I(beta 2 GP I), prothrombin, high- and low-molecular-weight kininogens, annexin V, protein C and protein S. In this article, the current knowledge on the methods of detection and their functional properties are reviewed, and the interaction of these antibodies and acquired activated protein C resistance are discussed.
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PMID:[Laboratory tests for detection of antiphospholipid antibodies]. 1139 41

Curcumin, in addition to its role as a spice, has been used for centuries to treat inflammatory disorders. Although the mechanism of action remains unclear, it has been shown to inhibit the activation of NF-kappaB and AP-1, transcription factors required for induction of many proinflammatory mediators. Due to its low toxicity it is currently under consideration as a broad anti-inflammatory, anti-tumor cell agent. In this study we investigated whether curcumin inhibited the response of gammadelta T cells to protease-resistant phosphorylated derivatives found in the cell wall of many pathogens. The results showed that curcumin levels > or =30 microM profoundly inhibited isopentenyl pyrophosphate-induced release of the chemokines macrophage inflammatory protein-1alpha and -1beta and RANTES. Curcumin also blocked isopentenyl pyrophosphate-induced activation of NF-kappaB and AP-1. Commencing around 16 h, treatment with curcumin lead to the induction of cell death that could not be reversed by APC, IL-15, or IL-2. This cytotoxicity was associated with increased annexin V reactivity, nuclear expression of active caspase-3, cleavage of poly(ADP-ribose) polymerase, translocation of apoptosis-inducing factor to the nucleus, and morphological evidence of nuclear disintegration. However, curcumin led to only large scale DNA chromatolysis, as determined by a combination of TUNEL staining and pulse-field and agarose gel electrophoresis, suggesting a predominantly apoptosis-inducing factor-mediated cell death process. We conclude that gammadelta T cells activated by these ubiquitous Ags are highly sensitive to curcumin, and that this effect may contribute to the anti-inflammatory properties of this compound.
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PMID:Curcumin inhibits activation of Vgamma9Vdelta2 T cells by phosphoantigens and induces apoptosis involving apoptosis-inducing factor and large scale DNA fragmentation. 1154 38

The family of autoantibodies known as antiphospholipid antibodies (aPL) and the lupus anticoagulant (LA) are associated with a spectrum of clinical manifestations including life-threatening thrombosis. While our current knowledge of thrombosis is imperfect and the mere presence of aPL is imprecisely associated with clinical events, our knowledge in this area has greatly expanded in recent years. It is clear that high levels of IgG aPL are associated with an increased risk of thrombosis. In 1990, investigators demonstrated that some aPL are directed against the beta2-Glycoprotein I (beta2-GPI) 50 kDa subunit and reported that these showed concordance with risk of clotting in certain groups of patients. Studies have also demonstrated that aPL reacted with antigens other than beta2-GPI, namely prothrombin, annexin V, protein S, protein C and high molecular weight kininogen. We review the clinical features of the antiphospholipid syndrome (APS), including vascular occlusion, pregnancy loss, thrombocytopenia and catastrophic APS. We also review the role of antibodies in the pathogenesis of APS as well as the spectrum of autoantibodies that have been found in APS.
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PMID:Antiphospholipid antibodies in systemic lupus erythematosus and the antiphospholipid syndrome. 1172 83

Disruption of the mouse gene encoding the blood coagulation inhibitor thrombomodulin (Thbd) leads to embryonic lethality caused by an unknown defect in the placenta. We show that the abortion of thrombomodulin-deficient embryos is caused by tissue factor-initiated activation of the blood coagulation cascade at the feto-maternal interface. Activated coagulation factors induce cell death and growth inhibition of placental trophoblast cells by two distinct mechanisms. The death of giant trophoblast cells is caused by conversion of the thrombin substrate fibrinogen to fibrin and subsequent formation of fibrin degradation products. In contrast, the growth arrest of trophoblast cells is not mediated by fibrin, but is a likely result of engagement of protease-activated receptors (PAR)-2 and PAR-4 by coagulation factors. These findings show a new function for the thrombomodulin-protein C system in controlling the growth and survival of trophoblast cells in the placenta. This function is essential for the maintenance of pregnancy.
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PMID:The thrombomodulin-protein C system is essential for the maintenance of pregnancy. 1261 68


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