THE SCAVENGER CELL PATHWAY FOR LIPOPROTEIN DEGRADATION - SPECIFICITY OF THE BINDING-SITE THAT MEDIATES THE UPTAKE OF NEGATIVELY-CHARGED LDL BY MACROPHAGES
THE SCAVENGER CELL PATHWAY FOR LIPOPROTEIN DEGRADATION - SPECIFICITY OF THE BINDING-SITE THAT MEDIATES THE UPTAKE OF NEGATIVELY-CHARGED LDL BY MACROPHAGES
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DOI：
10.1002/jss.400130107
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发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
GOLDSTEIN, JL
中科院分区：
文献类型：
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作者：
BROWN, MS;BASU, SK;GOLDSTEIN, JL
从几种动物（包括小鼠和大鼠）的多种器官中分离出的巨噬细胞表现出识别化学修饰蛋白的高亲和力结合位点。其中一个结合位点识别人血浆低密度脂蛋白（LDL），其中正电荷在。epsilon上。赖氨酸的-氨基被化学修饰去除或中和，从而使蛋白质具有增强的负电荷。有效的治疗方法包括LDL与有机酸酐反应（乙酰化或马来酰化）和与醛反应，如丙二醛处理。带负电荷的LDL与表面受体位点结合后，通过内吞作用被巨噬细胞迅速内化，并在溶酶体中水解。释放的胆固醇在细胞质中再酯化，产生大量胆固醇酯沉积。到目前为止，负电荷LDL的结合位点仅在巨噬细胞和其他清除细胞上被证实。在培养成纤维细胞、平滑肌细胞、淋巴细胞或肾上腺细胞中不表达。除了对乙酰化LDL和丙二醛处理的LDL具有亲和力外，巨噬细胞位点还能结合多种聚阴离子。它对某些硫酸酸化多糖（硫酸葡聚糖和岩藻油苷）、某些多核苷酸（聚肌苷酸和聚鸟苷酸）、聚乙烯醇硫酸盐和马来酰化白蛋白具有特别高的亲和力。与带负电荷的LDL结合的位点可能是导致血浆循环LDL水平高的患者巨噬细胞和其他清除细胞中胆固醇酯大量积累的原因。[本研究对家族性高胆固醇血症和动脉粥样硬化的适用性进行了讨论]。
Macrophages isolated from a variety of organs in several animal species [including mice and rats] exhibit high affinity binding sites that recognize chemically modified proteins. One of these binding sites recognizes human plasma low density lipoprotein (LDL) in which the positive charges on the .epsilon.-amino groups of lysine have been removed or neutralized by chemical modification, thus giving the protein an enhanced negative charge. Effective treatments include reaction of LDL with organic acid anhydrides (acetylation or maleylation) and reaction with aldehydes, such as treatment with malondialdehyde. After the negatively-charged LDL binds to the surface receptor sites, it is rapidly internalized by the macrophages by endocytosis and hydrolyzed in lysosomes. The liberated cholesterol is reesterified in the cytoplasm, producing massive cholesteryl ester deposition. The binding site for negatively-charged LDL has been demonstrated so far only on macrophages and other scavenger cells. It is not expressed in cultured fibroblasts, smooth muscle cells, lymphocytes or adrenal cells. In addition to its affinity for acetylated LDL and malondialdehyde-treated LDL, the macrophage site binds a variety of polyanions. It exhibits a particularly high affinity for certain sulfated polysaccharides (dextran sulfate and fucoidin), certain polynucleotides (polyinosinic acid and polyguanylic acid), polyvinyl sulfate and maleylated albumin. The site that binds negatively-charged LDL may be responsible for the massive accumulation of cholesteryl esters that occurs in macrophages and other scavenger cells in patients with high levels of circulating plasma LDL. [Applicability of this study to familial hypercholesterolemia and atherosclerosis was discussed].