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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL.
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Proatherogenic and proinflammatory properties of immune complexes prepared with purified human oxLDL antibodies and human oxLDL.

机译：用纯化的人oxLDL抗体和人oxLDL制备的免疫复合物的促动脉粥样硬化和促炎特性。

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摘要

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 micrograms) vs total cholesterol = 32.4-8.2 and cholesterol esters = 7.7 +/- 2.8 micrograms/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.
机译：用人低密度脂蛋白（LDL）和兔LDL抗体制备的免疫复合物（IC）诱导人巨噬细胞发生泡沫细胞转化，并激活人巨噬细胞和THP-1细胞促炎介质的释放。由于人氧化的LDL（oxLDL）抗体的亲和力低于兔抗体的亲和力，因此与人抗体形成的IC可能具有有限的致病性。使用先前在用兔抗体制备的LDL-IC特性研究中描述的两种方案，将由人氧化的LDL（oxLDL）和纯化的人oxLDL抗体（主要是IgG1和IgG3同种型）制备的免疫复合物呈递给THP-1细胞。通过吸附到红细胞（RBC）固定化的OxLDL /人oxLDL抗体IC导致THP-1细胞（872-313 pg / ml）释放的TNF水平明显高于吸附在RBC上的oxLDL（461-75.6 pg / ml） ），并在同一细胞中引起较高程度的胆固醇酯蓄积（与IC包覆的RBC孵育的细胞为5.4-0.77，而oxLDL包覆的RBC为1.99-1.16）。用oxLDL /人oxLDL抗体制备的不溶性IC能够更有效地促进THP-1细胞中胆固醇的细胞内积累（在不溶性IC孵育的THP-1细胞中，总胆固醇= 53.8-13.5，胆固醇酯= 24.0-7.2 mg / l （200毫克）vs总胆固醇= 32.4-8.2，胆固醇酯= 7.7 +/- 2.8微克/升（在以相同浓度的oxLDL孵育的THP-1细胞中），并且还诱导了TNF的释放。因此，我们证明了用人oxLDL和人oxLDL抗体制备的IC与用人LDL和兔LDL抗体制备的IC具有相同的致动脉粥样硬化和促炎特性。这强烈支持了循环和/或组织中存在的修饰的LDL-IC在动脉硬化中起重要的致病作用的概念。

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