抗リン脂質抗体症候群における動脈血栓の発症機序：β2-グリコプロテインIに特異的なリガンドと自己抗体の関与

β2-Glycoprotein I (β2-GPI) is a major antigen for anticardiolipin antibodies (aCL) appeared in patients with antiphospholipid syndrome (APS). We recently reported that β2-GPI specifically binds to oxidized low-density lipoprotein (oxLDL) and that on of the β2-GPI's major ligands derived from oxLDL, oxLig-1, is 9-(7-ketocholest-5-en-3β-yloxy)-9-oxononanoic acid (J. Lipid Res. 42, 697, 2001). In the present study, it was demonstrated that carboxylated variants of cholesteryl linoleate have a critical role for β2-GPI binding.In vitro experiments indicate that oxLDL was uptaken by macrophages via an interaction among the ligand such as oxLig-1, β2-GPI, and anti-β2-GPI autoantibodies. The uptake was not occurred by cholesterol or its ester without a free carboxyl residue, i.e., cholesteryl lenoleate, by cholesterol, or by 7-ketocholesterol alone, even in the presence of β2-GPI and anti-β2-GPI antibodies. Thus, carboxyl variants of cholesteryl ester specific for β2-GPI may mediate anti-β2-GPI Ab-dependent uptake of oxLDL by macrophages and autoimmune atherogenesis developed in APS.

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