Han J, Nicholson A C
Department of Pathology, Cornell University Medical College, New York, New York 10021, USA.
Am J Pathol. 1998 Jun;152(6):1647-54.
Macrophage scavenger receptors (MSR) bind and internalize oxidized low density lipoprotein (OxLDL), a modified lipoprotein that is thought to be the proximal source of lipids that accumulate within cells of atherosclerotic lesions. The role of lipoproteins in modulating MSR expression are undetermined. We studied the effect of lipoproteins, native and modified LDL (acetylated LDL (AcLDL) and OxLDL) on the expression of the MSR in RAW cells, a murine macrophage cell line. Exposure to lipoproteins resulted in a marked induction of MSR mRNA expression (12- to 17-fold) with OxLDL and AcLDL having the greatest effects. Maximum induction occurred 1 hour after treatment with OxLDL and LDL. AcLDL induced a fourfold increase at 1 hour followed by a return to baseline and peak expression (sixfold) at 14 hours. Scavenger receptor function, as measured by 125I-AcLDL binding, was only modestly increased in response to lipoproteins. Incubation of macrophages with a cholesterol acceptor particle resulted in a dose-dependent decrease in MSR mRNA expression, which paralleled cholesterol loss from the cells. OxLDL did not affect MSR mRNA stability, implying that MSR mRNA was transcriptionally regulated by lipoproteins. Finally, peritoneal macrophages were isolated from mice following intraperitoneal injection of lipoproteins. Macrophage expression of MSR mRNA was significantly (16-fold) increased by LDL, AcLDL, or OxLDL relative to mice infused with phosphate-buffered saline. This demonstration that exposure to lipoproteins increases expression of the macrophage scavenger receptor implies that lipoproteins can further contribute to foam cell development in atherosclerosis.
巨噬细胞清道夫受体（MSR）可结合并内化氧化型低密度脂蛋白（OxLDL），这种修饰的脂蛋白被认为是动脉粥样硬化病变细胞内积累脂质的主要来源。脂蛋白在调节MSR表达中的作用尚不确定。我们研究了天然和修饰的低密度脂蛋白（乙酰化低密度脂蛋白（AcLDL）和OxLDL）对RAW细胞（一种小鼠巨噬细胞系）中MSR表达的影响。暴露于脂蛋白会导致MSR mRNA表达显著诱导（12至17倍），其中OxLDL和AcLDL的影响最大。用OxLDL和LDL处理1小时后出现最大诱导。AcLDL在1小时时诱导增加四倍，随后恢复到基线，并在14小时达到峰值表达（六倍）。通过125I-AcLDL结合测量的清道夫受体功能仅对脂蛋白有适度增加。用胆固醇受体颗粒孵育巨噬细胞导致MSR mRNA表达呈剂量依赖性下降，这与细胞内胆固醇损失平行。OxLDL不影响MSR mRNA稳定性，这意味着MSR mRNA受脂蛋白转录调控。最后，在腹腔注射脂蛋白后从小鼠中分离出腹腔巨噬细胞。相对于注射磷酸盐缓冲盐水的小鼠，LDL、AcLDL或OxLDL使巨噬细胞MSR mRNA表达显著增加（16倍）。脂蛋白暴露会增加巨噬细胞清道夫受体的表达，这表明脂蛋白可进一步促进动脉粥样硬化中泡沫细胞的形成。
