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Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus

机译:系统性红斑狼疮患者循环祖细胞数量减少和功能受损

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摘要

Systemic lupus erythematosus (SLE) is associated with premature and accelerated atherosclerosis. Circulating progenitor cells (CPCs) are circulating bone-marrow derived cells that play an important role in the repair of vascular damage that underlies the development of atherosclerosis. The objective of this study was to determine the number and functionality of CPCs in patients with SLE. The study included 44 female SLE patients in an inactive stage of disease and 35 age-matched female controls. CPC numbers in the circulation were determined by FACS with monoclonals against CD14, CD34 and CD133. Peripheral blood-derived mononuclear cell (PBMNC) fractions were cultured in angiogenic medium. The endothelial-like phenotype was confirmed and the colony forming unit (CFU) capacity, migratory capacity and the potential to form clusters on Matrigel were determined. Expression of apoptosis inhibiting caspase 8L was analyzed in PBMNCs and CPCs by gene transcript and protein expression assays. The number of CD34–CD133 double-positive cells (P < 0.001) as well as the CFU capacity (P = 0.048) was reduced in SLE patients. Migratory activity on tumor necrosis factor-α tended to be reduced in patient CPCs (P = 0.08). Migration on vascular endothelial growth factor showed no significant differences, nor were differences observed in the potential to form clusters on Matrigel. The expression of caspase 8L was reduced at the transcriptional level (P = 0.049) and strongly increased at the protein level after culture (P = 0.003). We conclude that CPC numbers are reduced in SLE patients and functionality is partly impaired. We suggest these findings reflect increased susceptibility to apoptosis of CPCs from SLE patients.
机译:系统性红斑狼疮(SLE)与过早和加速的动脉粥样硬化相关。循环祖细胞(CPC)是源自骨髓的循环细胞,它们在修复动脉粥样硬化发展基础的血管损伤中起着重要作用。这项研究的目的是确定SLE患者中CPC的数量和功能。该研究纳入了处于疾病非活动期的44名女性SLE患者和35名年龄匹配的女性对照。通过FACS用针对CD14,CD34和CD133的单克隆抗体测定循环中的CPC数。在血管生成培养基中培养外周血来源的单核细胞(PBMNC)级分。确认了内皮样表型,并确定了集落形成单位(CFU)的能力,迁移能力和在Matrigel上形成簇的潜力。通过基因转录和蛋白表达分析法分析了PBMCCs和CPCs中抑制凋亡的半胱天冬酶8L的表达。 SLE患者的CD34–CD133双阳性细胞数量(P <0.001)和CFU容量(P = 0.048)减少。患者CPCs中对肿瘤坏死因子-α的迁移活性趋于降低(P = 0.08)。在血管内皮生长因子上的迁移无明显差异,在基质胶上形成簇的潜力也无差异。培养后,胱天蛋白酶8L的表达在转录水平降低(P = 0.049),在蛋白水平强烈升高(P = 0.003)。我们得出的结论是,SLE患者的CPC数量减少了,功能部分受损。我们建议这些发现反映了SLE患者对CPC凋亡的敏感性增加。

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