Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL
Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL
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DOI：
10.1006/clim.2002.5269
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发表时间：
2002-10-01
影响因子：
8.6
通讯作者：
Lopes-Virella, MF
中科院分区：
文献类型：
--
作者：
Virella, G;Atchley, D;Lopes-Virella, MF
用人低密度脂蛋白（LDL）和兔LDL抗体制备的免疫复合物（IC）诱导人巨噬细胞的泡沫细胞转化，并激活人巨噬细胞和THP-1细胞释放促炎介质。由于人氧化低密度脂蛋白（oxLDL）抗体的亲和力低于兔抗体，与人抗体形成的IC可能具有有限的致病潜力。使用先前在用兔抗体制备的LDL-IC的性质的研究中描述的两种方案，将用人氧化LDL（oxLDL）和纯化的人oxLDL抗体（主要是IgG 1和IgG 3同种型）制备的免疫复合物呈递给THP-1细胞。通过红细胞（RBC）吸附固定的oxLDL/人oxLDL抗体IC诱导THP-1细胞释放显著更高水平的TNF（872-313 pg/ml）比吸附于RBC的oxLDL（461-75.6 pg/ml），并在相同细胞中引起更高程度的胆固醇酯蓄积（在与IC包被的RBC孵育的细胞中为5.4-0.77，在oxLDL包被的RBC中为1.99-1.16）。用oxLDL/人oxLDL抗体制备的不溶性IC更有效地促进THP-1细胞内胆固醇的积累（在与不溶性IC（200 μ g）孵育的THP-1细胞中，总胆固醇= 53.8-13.5和胆固醇酯= 24.0-7.2 mg/l，而总胆固醇= 32.4-8.2和胆固醇酯= 7.7 +/- 2.8 μ g/l）。1在与相同浓度的oxLDL孵育的THP-1细胞中），并且还诱导TNF的释放。因此，我们已经证明，IC制备的人oxLDL和人oxLDL抗体具有相同的致动脉粥样硬化和促炎性的IC制备的人LDL和兔LDL抗体。这有力地支持了存在于循环和/或组织中的修饰的LDL-IC在动脉硬化中起重要致病作用的概念。(C)2002 Elsevier Science（美国）。
Immune complexes (IC) prepared with human low density lipoprotein (LDL) and rabbit LDL antibodies induce foam cell transformation of human macrophages and activate the release of proinflammatory mediators by human macrophages and THP-1 cells. Because the affinity of human oxidized LDL (oxLDL) antibodies is lower than that of rabbit antibodies, IC formed with human antibodies could have limited pathogenic potential. Immune complexes prepared with human oxidized LDL (oxLDL) and purified human oxLDL antibodies (predominantly of the IgG1 and IgG3 isotypes) were presented to THP-1 cells using two protocols previously described in studies of the properties of LDL-IC prepared with rabbit antibodies. OxLDL/human oxLDL antibody IC immobilized by adsorption to red blood cells (RBC) induced the release of significantly higher levels of TNF from THP-1 cells (872-313 pg/ml) than oxLDL adsorbed to RBC (461-75.6 pg/ml) and caused a higher degree of cholesterol ester accumulation in the same cells (5.4-0.77 in cells incubated with IC-coated RBC vs 1.99-1.16 in oxLDL-coated RBC). Insoluble IC prepared with oxLDL/human oxLDL antibody were even more effective in promoting intracellular accumulation of cholesterol in THP-1 cells (total cholesterol = 53.8-13.5 and cholesterol esters = 24.0-7.2 mg/l in THP-1 cells incubated with insoluble IC (200 jig) vs total cholesterol = 32.4-8.2 and cholesterol esters = 7.7 +/- 2.8 mug/l in THP-1 cells incubated with an identical concentration of oxLDL) and also induced the release of TNF. Thus we have demonstrated that IC prepared with human oxLDL and human oxLDL antibodies have the same atherogenic and proinflammatory properties as IC prepared with human LDL and rabbit LDL antibodies. This strongly supports the concept that modified LDL-IC present in circulation and/or tissues play an important pathogenic role in arteriosclerosis. (C) 2002 Elsevier Science (USA).