Involvement of beta(2)-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages
Involvement of beta(2)-glycoprotein I and anticardiolipin antibodies in oxidatively modified low-density lipoprotein uptake by macrophages
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DOI：
10.1046/j.1365-2249.1997.d01-948.x
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发表时间：
1997-03-01
影响因子：
4.6
通讯作者：
Koike, T
中科院分区：
文献类型：
--
作者：
Hasunuma, Y;Matsuura, E;Koike, T
抗磷脂综合征(APS)患者血清中的抗心磷脂抗体(ACL)识别β2-糖蛋白I(β2-GPI)与固相负电荷磷脂相互作用的结构改变。β(2)-GPI与Cu2+氧化型血浆脂蛋白结合，即氧化型极低密度脂蛋白(OxVLDL)、氧化型低密度脂蛋白(OxLDL)或氧化型高密度脂蛋白(OxHDL)。β2-GPI抑制小鼠巨噬细胞J774A.1细胞对oxLDL的体外摄取，即细胞表面结合、细胞结合和蛋白质降解。加入清道夫受体的竞争对手聚肌苷酸(Poly(I))可抑制oxLDL与巨噬细胞的结合，但另一种多阴离子酸多胞苷(PolyC)不能抑制oxLDL与巨噬细胞的结合。相反，同时加入人β(2)-GPI和来自APS动物模型NZW x BXSB F-1(WE F-1)小鼠的单克隆ACL，或由人β(2)-GPI免疫的BALB/c小鼠产生的抗β(2)-GPI抗体，可显著增加oxLDL的结合。这些结果表明，β(2)-GPI可能是一种抗动脉粥样硬化蛋白，针对β(2)-GPI的自身免疫反应可能在APS动脉粥样硬化的发生发展中起作用。
Anticardiolipin antibodies (aCL) in the sera of patients with antiphospholipid syndrome (APS) recognize an altered structure of beta 2-glycoprotein I (beta 2-GPI) interacting with solid-phase negatively charged phospholipids. beta(2)-GPI bound to Cu2+-oxidized plasma lipoproteins, i.e. oxidized very low-density lipoprotein (oxVLDL), oxidized low-density lipoprotein (oxLDL), or oxidized high-density lipoprotein (oxHDL). beta 2-GPI inhibited in vitro uptake, i.e. cell surface binding, cellular association, and proteolytic degradation of oxLDL by murine macrophage J774A.1 cells. The binding of oxLDL to the macrophages was inhibited by the addition of polyinosinic acid (poly (I)), a competitor of the scavenger receptor, but not by another polyanionic acid, polycytidylic acid (poly (C)). Conversely, the binding of oxLDL was significantly increased by the simultaneous addition of human beta(2)-GPI and monoclonal aCL derived from NZW x BXSB F-1 (WE F-1) mice, an animal model of APS, or anti-beta(2)-GPI antibodies from BALB/c mice immunized with human beta(2)-GPI. These findings indicate that beta(2)-GPI may be an antiatherogenic protein and that the autoimmune response against beta(2)-GPI may have a role in the development of atherosclerosis in APS.