The Role of Innate and Adaptive Immunity to Oxidized Low‐Density Lipoprotein in the Development of Atherosclerosis
The Role of Innate and Adaptive Immunity to Oxidized Low‐Density Lipoprotein in the Development of Atherosclerosis
复制标题
DOI：
10.1196/annals.1361.086
复制
发表时间：
2005-06
影响因子：
5.2
通讯作者：
Kazuko Kobayashi;L. R. Lopez;Y. Shoenfeld;E. Matsuura
中科院分区：
文献类型：
--
作者：
Kazuko Kobayashi;L. R. Lopez;Y. Shoenfeld;E. Matsuura
摘要：动脉粥样硬化是一种与全身和局部对各种抗原的免疫反应有关的慢性动脉壁炎症过程，其中氧化低密度脂蛋白(OxLDL)最为显著。氧化低密度脂蛋白的IgM和IgG抗体都是在动脉粥样硬化过程中产生的。一些研究表明，oxLDL抗体水平的升高与动脉粥样硬化的程度有关。其他研究报告称，用oxLDL免疫实验动物会诱导高水平的oxLDL抗体，从而减少动脉粥样硬化，这表明对oxLDL的免疫反应可能是抗动脉粥样硬化的。在系统性自身免疫性疾病患者中观察到动脉粥样硬化的加速发展。在抗磷脂综合征患者中，β2-糖蛋白I(β2GPI)是抗心磷脂抗体(ACL)的主要抗原靶点。我们最近报道，oxLDL与β2GPI通过氧化低密度脂蛋白衍生的特异性配体相互作用，如7-酮-胆固醇-9-羧氧基壬酸酯(oxLig-1)形成复合体。在体外，抗β2GPI自身抗体结合到oxLDL/β2GPI复合体上，这些复合体通过Fcγ受体被巨噬细胞主动摄取。检测了系统性红斑狼疮患者和AP患者外周血中oxLDL/β-2GPI复合体的水平，其水平均高于正常人。抗这些复合体的自身抗体也存在，但抗oxLig-1/β2GPI抗体水平在系统性红斑狼疮患者中显著高于非系统性红斑狼疮患者和健康人。
Abstract: Atherosclerosis is a chronic inflammatory process of the arterial wall associated with systemic and local immune responses to various antigens, oxidized low‐density lipoprotein (oxLDL) being the most significant. Both IgM and IgG antibodies to oxLDL are produced during atherosclerosis. Some studies have shown that elevated levels of antibody to oxLDL correlate with the degree of atherosclerosis. Other studies reported that immunization of experimental animals with oxLDL induces high levels of antibodies to oxLDL, with decreased atherosclerosis, suggesting that the immune response to oxLDL may be antiatherogenic. The accelerated development of atherosclerosis has been observed in patients with systemic autoimmune diseases. In patients with antiphospholipid syndrome (APS), β2‐glycoprotein I (β2GPI) is a major antigenic target for anticardiolipin antibodies (aCLs). We recently reported that oxLDL interacts with β2GPI via oxLDL‐derived specific ligands, such as 7‐ketocholesteryl‐9‐caboxynonanoate (oxLig‐1) to form complexes. In vitro, anti‐β2GPI autoantibodies bind to oxLDL/β2GPI complexes that are actively taken up by macrophages via Fcγ receptors. Circulating oxLDL/β2GPI complexes were detected in patients with systemic lupus erythematosus (SLE) and APS, at higher levels than in healthy individuals. Autoantibodies against these complexes were also present; however, IgG anti‐oxLig‐1/β2GPI antibody levels in SLE patients with APS were significantly higher than those in SLE patients without APS and those in healthy individuals.