Evidence of macrophage foam cell formation by very low-density lipoprotein receptor -: Interferon-γ inhibition of very low-density lipoprotein receptor expression and foam cell formation in macrophages
Evidence of macrophage foam cell formation by very low-density lipoprotein receptor -: Interferon-γ inhibition of very low-density lipoprotein receptor expression and foam cell formation in macrophages
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DOI：
10.1161/01.cir.103.8.1142
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发表时间：
2001-02-27
期刊：
影响因子：
37.8
通讯作者：
Miyamori, I
中科院分区：
文献类型：
--
作者：
Kosaka, S;Takahashi, S;Miyamori, I
背景-VLDL受体主要在巨噬细胞中的表达，已在人和兔的动脉粥样硬化病变中得到证实。针对巨噬细胞泡沫细胞形成机制中VLDL受体与残存颗粒的高亲和力，本研究探讨了干扰素-γ对佛波醇-12-肉豆蔻酸酯-13-醋酸酯(PMA)处理的THP-1、HL-60巨噬细胞和人单核细胞来源的巨噬细胞VLDL受体表达的影响，方法与结果-PMA诱导THP-1细胞分化为巨噬细胞。加入干扰素-γ，检测VLDL受体的表达，I-125-β-VLDL降解实验和油红O染色。在THP-1巨噬细胞中，VLDL受体蛋白的表达在PMA处理后2d开始下降，在3d开始升高，并持续到5d，清道夫受体蛋白在PMA处理后3d开始出现。干扰素-γ以剂量和时间依赖的方式抑制巨噬细胞VLDL受体的表达，但对单核细胞无抑制作用，而且在向巨噬细胞分化的过程中，干扰素-γ受体的mRNA表达增加，I-125-β-VLDL降解实验和油红O染色显示，干扰素-γ显著抑制摄取β-VLDL后泡沫细胞的形成。巨噬细胞不表达低密度脂蛋白受体相关蛋白(LRP)和低密度脂蛋白受体mRNAs，在PMA处理的HL-60巨噬细胞和人单核细胞来源的巨噬细胞中，干扰素-γ还抑制VLDL受体的表达和β-VLDL泡沫细胞的形成。结论单核-巨噬细胞分化过程中VLDL受体表达上调。干扰素-γ仅抑制巨噬细胞VLDL受体的表达和泡沫细胞的形成，残留颗粒通过VLDL受体途径诱导巨噬细胞泡沫细胞的形成。
Background-Expression of the VLDL receptor, primarily in macrophages, has been confirmed in human and rabbit atherosclerotic lesions. The high binding affinity of the VLDL receptor for remnant particles implicates the VLDL receptor pathway in the foam cell formation mechanism in macrophages, This study investigates the effect of interferon (IFN)-gamma on VLDL receptor expression in phorbol-12-myristate-13-acetate (PMA)-treated THP-1, HL-60 macrophages, and human monocyte-derived macrophages,Methods and Results-THP-1 cells were induced to differentiate into macrophages by PMA treatment. IFN-gamma was added to the medium, and expression of the VLDL receptor was determined, I-125-beta -VLDL degradation study and oil red O staining were examined. In THP-1 macrophages, VLDL receptor protein expression decreased at 2 days after PMA treatment but increased at 3 days and increased up to 5 days, Scavenger receptor proteins, which were not originally present, appeared at 3 days after PMA treatment. IFN-gamma inhibited VLDL receptor expression in a dose-and time-dependent manner in macrophages, However, no inhibitory effect was observed in monocytes, Moreover, IFN-gamma receptor mRNA increased during differentiation to macrophages, I-125-beta -VLDL degradation study and oil red O staining showed that IFN-gamma significantly inhibited foam cell formation after the uptake of beta -VLDL. LDL receptor-related protein (LRP) and LDL receptor mRNAs were not expressed in macrophages, In PMA-treated HL-60 macrophages and human monocyte-derived macrophages, IFN-gamma also inhibited VLDL receptor expression and foam cell formation by beta -VLDL.Conclusions-VLDL receptor expression is upregulated during monocyte-macrophage differentiation. IFN-gamma inhibits VLDL receptor expression and foam cell formation only in macrophages, Remnant particles induct macrophage foam cell formation through the VLDL receptor pathway.