DIFFERENTIAL EXPRESSION OF SCAVENGER RECEPTOR ISOFORMS DURING MONOCYTE-MACROPHAGE DIFFERENTIATION AND FOAM CELL-FORMATION
DIFFERENTIAL EXPRESSION OF SCAVENGER RECEPTOR ISOFORMS DURING MONOCYTE-MACROPHAGE DIFFERENTIATION AND FOAM CELL-FORMATION
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DOI：
10.1161/01.atv.14.5.798
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发表时间：
1994-05-01
期刊：
影响因子：
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通讯作者：
HANSSON, GK
中科院分区：
文献类型：
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作者：
GENG, YJ;KODAMA, T;HANSSON, GK
清道夫受体介导化学修饰脂蛋白的结合和摄取。通过对人巨噬细胞清道夫受体（MSR）的cDNA克隆，研究人员发现存在两种mRNA，即I型和II型，它们是由单个MSR基因的3'选择性剪接产生的，并被翻译成两种具有不同c端结构域的蛋白质。我们研究了从循环单核细胞到粘附巨噬细胞以及随后的脂质泡沫细胞分化过程中MSR异构体的表达。从单核细胞到巨噬细胞的分化与mRNA、蛋白质和细胞表面水平上MSR表达的显著增加有关，导致乙酰化低密度脂蛋白（LDL）的摄取增加。对mRNA和蛋白质的进一步分析表明，两种MSR亚型在CD14（+）外周血单核细胞表面以低且大致相等的数量存在；这些细胞具有大约相似水平的I型和II型MSR mRNA物种。在向巨噬细胞分化的过程中，I型MSR mRNA快速、选择性地增加，II型mRNA的表达水平与单核细胞大致相同。这反过来又导致单核细胞向巨噬细胞分化过程中细胞表面I型MSR蛋白的增加。在乙酰化LDL存在下，巨噬细胞向泡沫细胞转化过程中，I型MSR mRNA也占主导地位。这些发现表明，在单核细胞向巨噬细胞分化过程中，修饰LDL的摄取增加是通过I型MSRs在mRNA水平上的选择性上调来完成的。I型MSRs表达的增加可能对泡沫细胞的形成很重要。
Scavenger receptors mediate binding and uptake of chemically modified lipoproteins. cDNA cloning of the human macrophage scavenger receptor (MSR) reveals the presence of two mRNA species, the type I and II, isoforms, which are generated by 3' alternative splicing of a single MSR gene and translated into two proteins with different C-terminal domains. We studied MSR isoform expression during the differentiation from circulating monocytes to adherent macrophages and subsequently to lipid-laden foam cells. Differentiation from monocyte to macrophage was associated with a prominent increase in MSR expression on the mRNA, protein, and cell surface levels, leading to an increased uptake of acetylated low-density lipoprotein (LDL). Further analyses of mRNA and proteins revealed that both MSR isoforms were present in low and approximately equal amounts on the surface of CD14(+) peripheral blood monocytes; these cells had approximately similar levels of type I and type II MSR mRNA species. During differentiation to macrophages, there was a rapid, selective increase in type I MSR mRNA, with type II mRNA being expressed at approximately the same level as in the monocyte. This, in turn, resulted in an increase in type I MSR protein on the cell surface during differentiation from monocyte to macrophage. Type I MSR mRNA also dominated during the transformation of macrophages to foam cells in the presence of acetylated LDL. These findings suggest that the increased uptake of modified LDL during differentiation from monocyte to macrophage is accomplished by a selective upregulation of type I MSRs on the mRNA level. The increased expression of type I MSRs may be important for foam cell formation.