Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma
Extracellular matrix metalloproteinase inducer (EMMPRIN) is induced upon monocyte differentiation and is expressed in human atheroma
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DOI：
10.1161/01.atv.0000021411.53577.1c
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发表时间：
2002-07-01
影响因子：
8.7
通讯作者：
Bocan, TMA
中科院分区：
文献类型：
--
作者：
Major, TC;Liang, L;Bocan, TMA
由于细胞外基质金属蛋白酶诱导因子（EMMPRIN），一种肿瘤细胞衍生的蛋白质，诱导成纤维细胞中的基质金属蛋白酶（MMPs），并且因为MMPs在动脉粥样硬化形成中是重要的，我们研究了EMMPRIN是否在粒细胞/巨噬细胞集落刺激因子（GM-CSF）分化的人外周血单核细胞（HPBM）和巨噬细胞泡沫细胞中表达。此外，EMMPRIN研究了其在人类atheroams.Methods和结果的表达后，10天的GM-CSF诱导的单核细胞分化，EMMPRIN mRNA增加5至8倍，相对于未分化的单核细胞。GM-CSF处理HPBM显示EMMPRIN mRNA和蛋白在第2天比未分化的单核细胞上调。GM-CSF分化的HPBM表现出特征性的巨噬细胞表型，表现为煎饼样形态的增加和生化标志物如载脂蛋白E、MMP-9和胆固醇酯（CE）的增加。虽然乙酰化LDL处理10天的GM-CSF分化的HPBM增加CE质量13至321倍，EMMPRIN表达相对于非脂质负载的巨噬细胞没有变化。在人冠状动脉粥样硬化样本中，EMMPRIN在CD 68（+）巨噬细胞丰富的区域以及MMP-9 expressions. Conclusions的地区，我们得出结论，单核细胞分化诱导EMMPRIN表达，CE富集的泡沫细胞对EMMPRIN表达没有进一步的影响，EMMPRIN是存在于人类动脉粥样硬化。因此，EMMPRIN可能在动脉粥样硬化的发展中发挥作用。
Objective-Because extracellular matrix metalloproteinase inducer (EMMPRIN), a tumor cell-derived protein, induces matrix metalloproteinases (MMPs) in fibroblasts and because MMPs are important in atheroma formation, we investigated if EMMPRIN was expressed in granulocyte/macrophage-colony stimulating factor (GM-CSF)-differentiated human peripheral blood monocytes (HPBM) and macrophage foam cells. In addition, EMMPRIN was studied for its expression in human atheroma.Methods and Results-After 10 days of GM-CSF-induced monocyte differentiation, EMMPRIN mRNA increased 5- to 8-fold relative to undifferentiated monocytes. GM-CSF treatment of HPBM revealed that both EMMPRIN mRNA and protein were upregulated by day 2 over undifferentiated monocytes. GM-CSF-differentiated HPBM showed characteristic macrophage phenotype by showing increases in pancake-like morphology and increases in biochemical markers such as apolipoprotein E, MMP-9, and cholesterol ester (CE). While acetylated LDL treatment of the 10-day GM-CSF-differentiated HPBM increased CE mass 13- to 321-fold, EMMPRIN expression was unchanged relative to nonlipid-loaded macrophages. In human coronary atherosclerotic samples, EMMPRIN was observed in CD68(+) macrophage-rich areas as well as areas of MMP-9 expressions.Conclusions-Based on these data, we conclude that monocyte differentiation induces EMMPRIN expression, CE enrichment of foam cells has no further effect on EMMPRIN expression, and EMMPRIN is present in human atheroma. Therefore, EMMPRIN may play a role in atherosclerosis development.