Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages
Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages
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DOI：
10.1161/01.cir.103.8.1057
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发表时间：
2001-02-27
期刊：
影响因子：
37.8
通讯作者：
Matsuzawa, Y
中科院分区：
文献类型：
--
作者：
Ouchi, N;Kihara, S;Matsuzawa, Y
巨噬细胞中脂质的过度积累在动脉粥样硬化的发展中起着重要的作用。最近，我们发现了一种脂联素（adiponectin），这种脂联素在冠状动脉疾病患者中减少。我们之前证明脂联素作为促炎刺激的调节剂并抑制单核细胞与内皮细胞的粘附。本研究探讨了脂联素对人单核细胞衍生的macrophages.Methods和Results-human monocytes的脂质蓄积的影响，通过在人AB型血清中孵育7天，将人单核细胞分化为巨噬细胞，并在不同的时间间隔研究脂联素的影响。用生理浓度的脂联素治疗降低细胞内胆固醇酯含量，如使用酶。荧光法脂联素处理的巨噬细胞含有较少的油红O染色的脂滴。脂联素抑制A类巨噬细胞清道夫受体（MSR）的表达在mRNA和蛋白质水平的北方酸免疫印迹分析，分别，而不影响CD 36的表达，这是定量的流式细胞术。脂联素降低A类MSR启动子活性，如荧光素酶报告基因测定所测量。脂联素处理剂量依赖性地降低A类MSR配体结合和摄取活性。脂联素处理后，作为巨噬细胞分化标志的脂蛋白脂酶的mRNA水平降低，但载脂蛋白E的mRNA水平没有改变。脂联素周围的巨噬细胞在人受伤的主动脉immunoassociations.Conclusions-the脂肪细胞衍生的血浆蛋白脂联素抑制巨噬细胞到泡沫细胞的转化，这表明脂联素可能作为一个调制器巨噬细胞到泡沫细胞的转化。
Background-Excessive lipid accumulation in macrophages plays an important role in the development of atherosclerosis. Recently, we discovered an adipocyte-specific plasma protein, adiponectin, that is decreased in patients with coronary artery disease. We previously demonstrated that adiponectin acts as a modulator for proinflammatory stimuli and inhibits monocyte adhesion to endothelial cells. The present study investigated the effects of adiponectin on lipid accumulation in human monocyte-derived macrophages.Methods and Results-Human monocytes were differentiated into macrophages by incubation in human type AB serum for 7 days, and the effects of adiponectin were investigated at different rime intervals. Treatment with physiological concentrations of adiponectin reduced intracellular cholesteryl ester content, as determined using the enzymatic. fluorometric method. The adiponectin-treated macrophages contained fewer lipid droplets stained by oil red O. Adiponectin suppressed the expression of the class A macrophage scavenger receptor (MSR) at both mRNA and protein levels by Northern acid immunoblot analyses, respectively, without affecting the expression of CD36, which was quantified by flow cytometry. Adiponectin reduced the class A MSR promoter activity, as measured by luciferase reporter assay. Adiponectin treatment dose-dependently decreased class A MSR ligand binding and uptake activities. The mRNA level of lipoprotein lipase as a marker of macrophage differentiation was decreased by adiponectin treatment, but that of apolipoprotein E was not altered. Adiponectin was detected around macrophages in the human injured aorta by immunohistochemistry.Conclusions-The adipocyte-derived plasma protein adiponectin suppressed macrophage-to-foam cell transformation, suggesting that adiponectin may act as a modulator for macrophage-to-foam cell transformation.