Activation of peripheral blood CD14+ monocytes occurs in diabetes

Activation of peripheral blood CD14+ monocytes occurs in diabetes
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DOI:
10.2337/diabetes.54.9.2779
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发表时间:
2005-09-01
期刊:
影响因子:
7.7
通讯作者:
Trimble, ER
Trimble, ER
中科院分区:
医学1区
文献类型:
--
作者:
Cipolletta, C;Ryan, KE;Trimble, ER

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与内皮功能障碍和动脉粥样硬化相关的炎症标志物的血液水平在糖尿病患者中增加;最高水平发生在控制不良的糖尿病患者中。我们研究了糖尿病患者外周血单核细胞清道夫受体(CD 36)表达和单核细胞趋化蛋白-1,细胞内粘附分子-1,血管细胞粘附分子-1和过氧化物酶体增殖物激活受体mRNA表达的激活状态。从血糖控制良好(HbA 1c 9.4%)的1型和2型糖尿病患者和一组非糖尿病受试者的外周血中分离CD 14(+)单核细胞。糖尿病患者的单核细胞显示CD 36细胞表面表达增加(P < 0.0005)和氧化LDL摄取增加(P < 0.05)。单核细胞趋化蛋白-1基因在两组糖尿病患者单核细胞中的表达均增加(P < 0.05)。在控制不良的糖尿病组中,CD 68和过氧化物酶体增殖物激活受体-γ基因表达均增加(各P < 0.05),其单核细胞也显示出与内皮单层的粘附增加(与非糖尿病对照受试者相比P < 0.0005)。在控制不佳的糖尿病中,CD 14(+)单核细胞功能性活化,并显示出与巨噬细胞相关的一些分化标志物。这些单核细胞还表现出附着于正常内皮细胞的能力增加,这是动脉粥样硬化形成的早期阶段之一。
Blood levels of inflammatory markers associated with endothelial dysfunction and atherosclerosis are increased in diabetic patients; the highest levels occur in poorly controlled diabetes. We investigated the activation state of peripheral blood monocytes in diabetes with respect to scavenger receptor (CD36) expression and monocyte chemoattractant protein-1, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and peroxisome proliferator-activated receptors mRNA expression. CD14(+) monocytes were isolated from peripheral blood of type 1 and type 2 diabetic patients with good (HbA(1c) 9.4%) glycemic control and a group of nondiabetic subjects. Monocytes from diabetic subjects displayed increased CD36 cell surface expression (P < 0.0005) and increased uptake of oxidized LDL (P < 0.05). Monocyte chemoattractant protein-1 gene expression was increased in monocytes from both groups of diabetic subjects (P < 0.05). Both CD68 and peroxisome proliferator-activated receptor-gamma gene expression were increased in the poorly controlled diabetic group (P < 0.05 for each), whose monocytes also displayed increased attachment to endothelial monolayers (P < 0.0005 vs. nondiabetic control subjects). In poorly controlled diabetes, CD14(+) monocytes are functionally activated and show some of the differentiation markers associated with macrophages. These monocytes also demonstrate an increased ability for attachment to normal endothelial cells, one of the early stages in atherogenesis.