Expression of class A scavenger receptor inhibits apoptosis of macrophages triggered by oxidized low density lipoprotein and oxysterol
Expression of class A scavenger receptor inhibits apoptosis of macrophages triggered by oxidized low density lipoprotein and oxysterol
复制标题
DOI：
10.1161/01.atv.20.8.1968
复制
发表时间：
2000-08-01
影响因子：
8.7
通讯作者：
Geng, YJ
中科院分区：
文献类型：
--
作者：
Liao, HS;Kodama, T;Geng, YJ
A类巨噬细胞清道夫受体（MSR-A）是一种多功能的三聚体糖蛋白，参与先天性免疫反应以及动脉粥样硬化过程中载脂泡沫细胞的发育。已知MSR配体氧化低密度脂蛋白（oxLDL）对巨噬细胞和其他细胞类型具有细胞毒性。本研究检查了MSR是否介导或调节oxLDL诱导的细胞凋亡。用oxLDL及其细胞毒性氧化固醇、7-酮胆固醇（7-KC）处理，可降低人THP-1细胞、中国仓鼠卵巢细胞和小鼠腹腔巨噬细胞的活力并增加DNA片段化。然而，细胞死亡和DNA断裂显着减少佛波酯分化的MSR-expressing THP-1细胞和中国仓鼠卵巢细胞，与稳定表达MSR-AI cDNA转染后暴露于相同浓度的oxLDL和7-KC。此外，与野生型巨噬细胞相比，用oxLDL和7-KC处理诱导MSR-A缺陷型腹腔巨噬细胞更大的死亡和DNA片段化。因此，MSR-A不作为负责oxLDL的凋亡效应的受体，相反，该受体的表达赋予巨噬细胞对oxLDL及其细胞毒性脂质组分的凋亡刺激的抗性。这些结果表明，通过防止细胞凋亡，MSR-A可能有助于动脉粥样硬化病变中巨噬细胞和巨噬细胞衍生的载脂泡沫细胞的长期存活。
The class A macrophage scavenger receptor (MSR-A) is a multifunctional trimeric glycoprotein involved in innate immune response as well as the development of lipid-laden foam cells during atherosclerosis. The MSR ligand, oxidized low density lipoprotein (oxLDL), is known to be cytotoxic to macrophages and other cell types. This study examined whether MSR mediates or modulates oxLDL-induced apoptosis. Treatment with oxLDL and its cytotoxic oxysterol, 7-ketocholesterol (7-KC), reduced viability and increased DNA fragmentation in human THP-1 cells, Chinese hamster ovary cells, and mouse peritoneal macrophages. However, cell death and DNA fragmentation were markedly diminished in the phorbol ester-differentiated MSR-expressing THP-1 cells and Chinese hamster ovary cells, with stable expression of MSR-AI after cDNA transfection when exposed to the same concentrations of oxLDL and 7-KC. Moreover, treatment with oxLDL and 7-KC induced much greater death and DNA fragmentation in MSR-A-deficient peritoneal macrophages compared with wild-type macrophages. Thus, MSR-A does not act as a receptor responsible for the apoptotic effect of oxLDL, and instead, expression of this receptor confers resistance of macrophages to the apoptotic stimulation by oxLDL and its cytotoxic lipid component. These results suggest that by preventing apoptosis, MSR-A may contribute to the long-term survival of macrophages and macrophage-derived lipid-laden foam cells in atherosclerotic lesions.