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• W4313343497 endingPage "5578" @default.
• W4313343497 startingPage "5572" @default.
• W4313343497 abstract "Abstract β2-Glycoprotein I (β2GPI) is a phospholipid-binding protein recognized by serum autoantibodies from the anti-phospholipid syndrome both in cardiolipin- and β2GPI-coated plates. We found that: 1) recombinant wild-type β2GPI bound to HUVEC and was recognized by both human monoclonal IgM and affinity-purified polyclonal IgG anti-β2GPI anti-phospholipid syndrome Abs; and 2) a single amino acid change from Lys286 to Glu significantly reduced endothelial adhesion. Double and triple mutants (from Lys284,287 to Glu284,287, from Lys286,287 to Glu286,287, and from Lys284,286,287 to Glu284,286,287) completely abolished endothelial binding. A synthetic peptide (P1) spanning the sequence Glu274–Cys288 of the β2GPI fifth domain still displayed endothelial adhesion. Another peptide (P8), identical with P1 except that Cys281 and Cys288 were substituted with serine residues, did not bind to HUVEC. Anti-β2GPI Abs, once bound to P1 adhered to HUVEC, induced E-selectin expression and up-regulated IL-6 secretion. Control experiments conducted with irrelevant Abs as well as with the P8 peptide did not show any endothelial Ab binding nor E-selectin and IL-6 modulation. Our results suggest that: 1) β2GPI binds to endothelial cells through its fifth domain; 2) the major phospholipid-binding site that mediates the binding to anionic phospholipids is also involved in endothelial binding; 3) HUVEC provide a suitable surface for β2GPI binding comparable to that displayed by anionic phospholipids dried on microtiter wells; and 4) the formation of the complex between β2GPI and the specific Abs leads to endothelial activation in vitro." @default.
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• W4313343497 date "1998-06-01" @default.
• W4313343497 modified "2023-10-14" @default.
• W4313343497 title "Human β2-Glycoprotein I Binds to Endothelial Cells Through a Cluster of Lysine Residues That Are Critical for Anionic Phospholipid Binding and Offers Epitopes for Anti-β2-Glycoprotein I Antibodies" @default.
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• W4313343497 doi "https://doi.org/10.4049/jimmunol.160.11.5572" @default.
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