Zhou X, Caligiuri G, Hamsten A, Lefvert A K, Hansson G K
Centre for Molecular Medicine and King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden.
Arterioscler Thromb Vasc Biol. 2001 Jan;21(1):108-14. doi: 10.1161/01.atv.21.1.108.
Atherosclerosis is an inflammatory disease, and the involvement of immune mechanisms in disease progression is increasingly recognized. Immunization with oxidized low density lipoprotein (LDL) decreases atherosclerosis in several animal models. To explore humoral and cellular immune reactions involved in this protection, we immunized apolipoprotein E knockout mice with either homologous plaque homogenates or homologous malondialdehyde (MDA)-LDL. Immunization with both these antigen preparations reduced lesion development. The plaques contained immunogen(s) sharing epitopes on MDA-LDL, MDA-very low density lipoprotein, and oxidized cardiolipin. This shows that a T-cell-dependent antibody response was associated with protection against atherosclerosis. The protection was associated with specific T-cell-dependent elevation of IgG antibodies against MDA-LDL and oxidized phospholipids, and the increased titers of IgG antibodies were correlated with decreased lesion formation and lower serum cholesterol levels.
动脉粥样硬化是一种炎症性疾病，免疫机制在疾病进展中的作用越来越受到认可。在几种动物模型中，用氧化型低密度脂蛋白（LDL）进行免疫可减轻动脉粥样硬化。为了探究这种保护作用中涉及的体液免疫和细胞免疫反应，我们用同源斑块匀浆或同源丙二醛（MDA）-LDL对载脂蛋白E基因敲除小鼠进行免疫。用这两种抗原制剂进行免疫均可减少病变发展。这些斑块含有在MDA-LDL、MDA-极低密度脂蛋白和氧化型心磷脂上具有共同表位的免疫原。这表明T细胞依赖性抗体反应与抗动脉粥样硬化保护作用相关。这种保护作用与针对MDA-LDL和氧化磷脂的IgG抗体的特异性T细胞依赖性升高有关，并且IgG抗体滴度的增加与病变形成减少和血清胆固醇水平降低相关。
