Comparative study on circulating endothelial progenitor cells in systemic lupus erythematosus patients at active stage
Comparative study on circulating endothelial progenitor cells in systemic lupus erythematosus patients at active stage
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系统性红斑狼疮活动期患者循环内皮祖细胞的比较研究
DOI：
10.1007/s00296-009-1156-4
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Liu, Rui
中科院分区：
文献类型：
--
作者：
Deng, Xiao Li;Li, Xiao Xia;Liu, Rui
循环内皮祖细胞（CEPCs）在动脉粥样硬化的过程中起着重要的作用。以往对系统性红斑狼疮（SLE）患者CEPC的研究多集中在其数量和部分功能上，结果不一致。关于其抗炎作用和整合状态的研究未见报道。本研究的目的是确定活动性SLE患者CEPC的数量、功能（包括抗炎功能）和整合状态。该研究在35名活动性SLE患者（28名女性，7名男性）和35名年龄和性别匹配的健康对照中进行。CEPC数量通过细胞活化细胞分选法测定。增殖细胞核抗原（PCNA）染色检测CEPC的增殖能力。采用细胞粘附实验检测CEPC与纤维连接蛋白的粘附能力和THP 1细胞与CEPC的粘附能力。通过transwell小室测定来测量CEPC的迁移能力，并且通过在Matrigel测试上的体内管形成来确定CEPC在Matrigel上形成管的潜力。采用定量PCR检测诱导型一氧化氮合酶（iNOS）和白细胞介素6（IL-6）的表达，Western印迹检测细胞间粘附分子1（ICAM-1）和磷酸化Akt（p-Akt）的表达，评价CEPCs的抗炎作用和细胞状态。SLE患者CEPC的数量与对照组比较无显著性差异（p> 0.05）。活动期SLE患者CEPC的增殖能力降低（p= 0.027）。SLE患者CEPC与纤维连接蛋白的粘附能力降低（p= 0.04），而THP 1细胞与CEPC的粘附能力增加（p< 0.001）。患者CEPC的迁移活性降低（p< 0.001）。SLE患者CEPCs在Matrigel上的成管能力降低（P< 0.001）。SLE患者CEPC中iNOS、IL-6（分别为p<0.001，p = 0.006）和ICAM-1的表达均升高，p-Akt的表达降低。我们的数据显示，活动性SLE患者的CEPC数量与健康对照组无显著差异，但其功能部分受损，包括增殖，粘附，迁移和管形成。在我们的研究中还观察到活动性SLE中CEPCs的不良细胞状态和对炎症过程的易感性增加。
Circulating endothelial progenitor cells (CEPCs) play an important role in the process of atherosclerosis. Most previous studies on CEPC in systemic lupus erythematosus (SLE) patients were on their number and some functions and the results were not consistent. No studies on their anti-inflammatory function and integrated status were reported. The purpose of this study was to determine the number, function (including anti-inflammatory function), and the integrated status of CEPCs in active SLE patients. The study was performed in 35 active SLE patients (28 females, 7 males) and 35 age-and gender-matched healthy controls. CEPC number was determined by Fluorescence-Activated Cell Sorting. Proliferation capacity of CEPC was assessed by PCNA staining. Adhesion capacity of CEPC to fibronectin and adhesion capacity of THP1 cell to CEPC were determined by cell adhesion assay. Migratory capacity of CEPC was measured by transwell chamber assay and the potential to form tubes on Matrigel of CEPC was determined by in vivo tube formation on Matrigel test. The expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) assessed by quantitative PCR as well as the expression of intercellular adhesion molecule-1 (ICAM-1) and phosphorylated-Akt (p-Akt) assessed by western-blotting were used to evaluate the anti-inflammatory function and cell status of CEPCs. The number of CEPC in SLE patients was not different from that in control (p> 0.05). Proliferation capacity of CEPC was decreased in active SLE patients (p= 0.027). Adhesion capacity of CEPC to fibronectin was decreased (p= 0.04) in SLE patients and adhesion capacity of THP1 cell to CEPC was increased in SLE patients (p< 0.001). Migratory activity was reduced in patient CEPCs (p< 0.001). Capacity of CEPCs to form tube on Matrigel was decreased in SLE patients (p< 0.001). Expression of iNOS and IL-6 (p< 0.001,p= 0.006, respectively) and ICAM-1 were increased in CEPC of SLE patients and expression of p-Akt was decreased in CEPC of SLE patients. Our data show that CEPC number in active SLE patients was not significantly different from healthy controls, but their functions were partly impaired, including proliferation, adhesion, migration, and tube formation. Bad cell status and increased susceptibility to inflammatory process of CEPCs in active SLE were also observed in our study.