Monoclonal antibodies against LDL further enhance macrophage uptake of LDL aggregates.
Monoclonal antibodies against LDL further enhance macrophage uptake of LDL aggregates.
复制标题
抗 LDL 的单克隆抗体进一步增强巨噬细胞对 LDL 聚集体的摄取。
DOI：
10.1161/01.atv.12.11.1258
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Witztum,JL
中科院分区：
文献类型：
--
作者：
Khoo,JC;Miller,E;Pio,F;Steinberg,D;Witztum,JL
低密度脂蛋白（LDL）的自聚集体比天然LDL更快地被巨噬细胞吸收和降解。这种增强的摄取部分归因于通过LDL受体途径的吞噬作用。然而，动脉巨噬细胞似乎表达很少的LDL受体活性。目前的研究表明，LDL聚集体可能有助于泡沫细胞形成的另一种机制。这可能通过形成大的免疫复合物而发生，所述免疫复合物通过Fc受体被巨噬细胞摄取。当用天然可溶性LDL和MB 47（一种对LDL受体识别的载脂蛋白B结构域特异的单克隆抗体）形成免疫复合物时，与单独的天然LDL相比，巨噬细胞随后对LDL的摄取和降解被抑制50-80%。相比之下，当聚集的LDL以相似的摩尔比与MB 47结合时，不溶性免疫复合物的随后降解比单独的聚集的LDL的降解大2 - 5倍。当MB 47的Fab或F（ab '）2片段取代完整抗体时，增强的摄取被消除，表明增加的摄取是通过Fc受体途径。此外，通过与热聚集免疫球蛋白竞争Fc受体，降低了聚集LDL的免疫复合物的摄取。细胞胆固醇酯化率也增加，巨噬细胞胆固醇酯质量也增加。由于LDL的聚集体以及抗修饰LDL的自身抗体已在动脉粥样硬化病变中得到证实，因此可能在内膜中产生修饰LDL聚集体的免疫复合物。（250字处删节）
Self-aggregates of low density lipoprotein (LDL) are taken up and degraded more rapidly by macrophages than is native LDL. That enhanced uptake is attributable in part to phagocytosis via the LDL receptor pathway. However, arterial macrophages appear to express little LDL receptor activity. The present studies demonstrate an alternative mechanism by which LDL aggregates could contribute to foam cell formation. This could occur by the formation of large immune complexes that are taken up by macrophages via the Fc receptor. When immune complexes were formed with native, soluble LDL and MB47, a monoclonal antibody specific to the apoprotein B domain recognized by the LDL receptor, the subsequent uptake and degradation of the LDL by macrophages were inhibited 50-80% compared with native LDL alone. In contrast, when aggregated LDL was bound to MB47 at a similar molar ratio, the subsequent degradation of the insoluble immune complexes was two- to fivefold greater than that of aggregated LDL alone. The enhanced uptake was abolished when Fab or F(ab')2 fragments of MB47 were substituted for the intact antibody, indicating that the increased uptake was via the Fc receptor pathway. Furthermore, the uptake of the immune complexes of aggregated LDL was reduced by competition for the Fc receptor with heat-aggregated immunoglobulin. There was also an increase in the rate of cellular cholesterol esterification and an increase in macrophage cholesteryl ester mass. Since aggregates of LDL as well as autoantibodies against modified LDL have been demonstrated in atherosclerotic lesions, it is possible that immune complexes of aggregates of modified LDL may be generated in the intima.(ABSTRACT TRUNCATED AT 250 WORDS)