细胞外基质金属蛋白酶诱导剂(EMMPRIN)诱导单核细胞分化并在人动脉粥样硬化中表达

T. Major, L. Liang, Xiao-Dong Lu, W. Rosebury, T. Bocan
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引用次数: 108

摘要

目的:由于细胞外基质金属蛋白酶诱导剂(EMMPRIN)是一种肿瘤细胞来源的蛋白,可在成纤维细胞中诱导基质金属蛋白酶(MMPs),并且MMPs在动脉粥样硬化形成中起重要作用,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,我们还研究了EMMPRIN在人动脉粥样硬化中的表达。方法和结果:gm - csf诱导单核细胞分化10天后,EMMPRIN mRNA相对于未分化的单核细胞增加5- 8倍。GM-CSF对HPBM的处理显示,在未分化的单核细胞中,EMMPRIN mRNA和蛋白在第2天均上调。gm - csf分化的HPBM表现出特征性巨噬细胞表型,表现为煎饼样形态增加,生化标志物如载脂蛋白E、MMP-9和胆固醇酯(CE)增加。虽然乙酰化LDL处理10天gm - csf分化的HPBM使CE质量增加13- 321倍,但相对于非脂质负载的巨噬细胞,EMMPRIN的表达没有变化。在人冠状动脉粥样硬化样品中,在CD68(+)巨噬细胞富集区和MMP-9表达区观察到EMMPRIN。结论:单核细胞分化诱导EMMPRIN表达,泡沫细胞CE富集对EMMPRIN表达无进一步影响,EMMPRIN在人动脉粥样硬化中存在。因此,EMMPRIN可能在动脉粥样硬化的发展中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Is Induced Upon Monocyte Differentiation and Is Expressed in Human Atheroma
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.
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