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)

The binding and uptake of phosphatidylserine (PS)-expressing cells appears to involve multiple receptor-mediated systems that recognize the lipid either directly or indirectly through intermediate proteins that form a molecular bridge between the cells. Here we show that beta2-glycoprotein I (beta2GPI), a 50-kDa serum glycoprotein, binds PS-containing vesicles and serves as an intermediate for the interaction of these vesicles with macrophages. Chemical modification of lysines and cysteines abolished beta2GPI-dependent PS uptake by inhibiting the binding of PS to beta2GPI and the binding of PS.beta2GPI complex to macrophages, respectively. Recognition was mediated by beta2GPI and not by the lipid because antibodies to beta2GPI inhibited binding of the complex to macrophages. These results indicate that human (THP-1-derived) macrophages bind beta2GPI only after it is bound to its lipid ligand. Competition experiments with monosaccharides that inhibit lectin-dependent interactions, and PS.beta2GPI binding experiments using deglycosylated beta2GPI, suggested that carbohydrate residues were not required for macrophage recognition of the complex. Antibodies to putative macrophage PS receptors (CD36, CD68, and CD14) did not inhibit uptake of the complex. These data suggest that beta2GPI can bind cells that fail to maintain membrane lipid asymmetry and generate a specific bridging moiety that is recognized for clearance by a phagocyte receptor that is distinct from CD36, CD68, and CD14.
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PMID:Characterization of phosphatidylserine-dependent beta2-glycoprotein I macrophage interactions. Implications for apoptotic cell clearance by phagocytes. 978 40

Treatment with the antimalarial drug hydroxychloroquine (HCQ) has been associated with reduced risk of thrombosis in the antiphospholipid (aPL) syndrome (APS) and, in an animal model of APS, with reduction of experimentally induced thrombosis. Recognition of beta2-glycoprotein I (beta2GPI) by aPL antibodies appears to play a major role in the disease process. We therefore used the techniques of ellipsometry and atomic force microscopy (AFM) to investigate whether HCQ directly affects the formation of aPL IgG-beta2GPI complexes on phospholipid bilayers. HCQ, at concentrations of 1 mug/mL and greater, significantly reduced the binding of aPL-beta2GPI complexes to phospholipid surfaces and THP-1 (human acute monocytic leukemia cell line) monocytes. The drug also reduced the binding of the individual proteins to bilayers. This HCQ-mediated reduction of binding was completely reversed when the HCQ-protein solutions were dialyzed against buffer. HCQ also caused modest, but statistically significant, reductions of clinical antiphospholipid assays. In conclusion, HCQ reduces the formation of aPL-beta2GPI complexes to phospholipid bilayers and cells. This effect appears to be due to reversible interactions between HCQ and the proteins and may contribute to the observed reduction of thrombosis in human and experimental APS. These results support the possibility that HCQ, or analogous molecules, may offer novel nonanticoagulant therapeutic strategies for treating APS.
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PMID:Hydroxychloroquine directly reduces the binding of antiphospholipid antibody-beta2-glycoprotein I complexes to phospholipid bilayers. 1857 8

Growing evidence suggests that autoantibodies directly contribute to hypercoagulability in the antiphospholipid syndrome (APS). One proposed mechanism is the antibody-induced expression of tissue factor (TF) by blood monocytes. Annexin A2 (ANX2), a mediator of cell surface-specific plasmin generation, was identified to mediate endothelial cell activation by anti-beta2-glycoprotein I (anti-beta 2 GPI) antibody. Our previous study suggested that ANX2 was also involved in anti-beta 2 GPI/beta 2 GPI-induced TF expression on monocytes. In the current study, it was further demonstrated that beta 2 GPI interacts with ANX2 not only in a cell-dependent form but also in a cell-free system. To further confirm the effects of ANX2 on anti-beta 2 GPI/beta 2 GPI-induced TF expression, an ANX2 cDNA-containing vector was transfected into HEK 293T cells which had originally little ANX2, then cells were treated by anti-beta 2 GPI/beta 2 GPI complex. It was found that transfected HEK 293T cells could express more TF both at mRNA and protein levels than that of no-transfected cells. On the other hand, the TF expression was dramatically decreased in the THP-1 cells in which the ANX2 RNA interference was performed. In conclusion, these results indicate that ANX2 on cell surface functions as a mediator boosting TF expression on monocytes induced by anti-beta 2 GPI/beta 2 GPI complex, which is contributed to the thrombotic events in APS.
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PMID:Annexin A2 mediates anti-beta 2 GPI/beta 2 GPI-induced tissue factor expression on monocytes. 1972 97

The majority of the antiphospholipid antibodies, present in patients with antiphospholipid syndrome, are directed against conformational epitopes in beta2-glycoprotein I. beta2-glycoprotein I is an anionic phospholipid-binding 50-kDa plasma protein whose physiological role is not clear. Here we investigate the role of beta2-glycoprotein I in the phagocytosis of phosphatidylserine-expressing platelet microvesicles and the effect of autoantibodies to beta2-glycoprotein I on this process. We labelled the glycans of beta2-glycoprotein I with BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene)-hydrazide without affecting its phospholipid binding capacity. BODIPY-beta2-glycoprotein I bound to platelet microvesicles in a concentration-dependent manner and promoted the phagocytosis of platelet microvesicles by THP-1 derived macrophages in vitro at physiological plasma concentrations with a half maximal effect at approximately 10 microg/ml. beta2-glycoprotein I-stimulated phagocytosis was inhibited by annexin A5 and the phosphatidylserine-binding C1C2 fragment of lactadherin. Furthermore, immunoaffinity purified beta2-glycoprotein I-dependent antiphospholipid antibodies from five patients with antiphospholipid syndrome inhibited the phagocytosis in a concentration-dependent manner. These studies suggest that the binding of beta2-glycoprotein I to phosphatidylserine-expressing procoagulant platelet microvesicles may promote their clearance by phagocytosis and autoantibodies to beta2-glycoprotein I may inhibit this process to induce a procoagulant state.
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PMID:Phagocytosis of platelet microvesicles and beta2- glycoprotein I. 2053 17