Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis
Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis
复制标题
DOI：
10.1053/j.ajkd.2004.10.022
复制
发表时间：
2005-02-01
影响因子：
13.2
通讯作者：
Aljama, P
中科院分区：
文献类型：
--
作者：
Ramírez, R;Carracedo, J;Aljama, P
背景：由于频繁的激活诱导复制，反复刺激的单核细胞可能会过早衰老。在血液透析患者中，单个核细胞在每次血液透析过程中被反复激活。衰老单核细胞的特征包括端粒长度缩短，p53表达增加，CD14dim/CD16bright表达增加，白细胞介素过量产生。方法：对15例血液透析患者和15例年龄匹配的对照组外周血单核细胞进行评价。用流式细胞术中的荧光原位杂交法测定端粒长度。通过使用特异性抗体的流式细胞术评估p53、CD14/CD16的表达和细胞内细胞因子（白细胞介素-1 β [IL-1 β]、IL-6和IL-4）的产生。结果：在单个核细胞亚群中发现衰老的特征：(1)端粒缩短加速，(2)p53表达增加，(3)CD14dim/CD16bright表达增加，(4)细胞因子（IL-1 β， IL-6和IL-4）过量产生。40% +/- 6%的血液透析患者细胞端粒长度缩短，而年龄匹配的对照组不到5%。短端粒细胞百分比与血清c反应蛋白水平呈正相关，反映炎症。血液透析患者单核细胞中P53表达升高。端粒长度减少的血液透析患者单核细胞主要表现为CD14dim/CD16bright表型；相反，端粒正常的细胞呈现CD14bright/CD16dim表型。最后，血液透析患者而非对照组的单核细胞自发产生促炎细胞因子IL-1 β和IL-6。结论：本研究显示血液透析患者外周血单核细胞存在过早衰老亚群。这些衰老细胞可能是反复激活的结果，可能在血液透析患者的慢性炎症中起病理生理作用。
Background: Repeatedly stimulated mononuclear cells may become senescent prematurely as a result of frequent activation-induced replication. In hemodialysis patients, mononuclear cells are activated repeatedly with each hemodialysis procedure. Characteristics of senescent mononuclear cells include telomere length shortening, increased p53 expression, CD14dim/CD16bright expression, and interleukin overproduction. Methods: Peripheral mononuclear cells from 15 hemodialysis patients and 15 age-matched controls were evaluated. Telomere length was assessed by means of fluorescence in situ hybridization in flow cytometry. Expression of p53, CD14/CD16, and intracellular cytokine production (interleukin-1 beta [IL-1 beta], IL-6, and IL-4) was evaluated by means of flow cytometry using specific antibodies. Results: Features of senescence were found in a subpopulation of mononuclear cells: (1) accelerated telomere shortening, (2) increased p53 expression, (3) CD14dim/CD16bright expression, and (4) cytokine overproduction (IL-1 beta, IL-6, and IL-4). Telomere length shortening was present in 40% +/- 6% of cells from hemodialysis patients compared with less than 5% from age-matched controls. Percentage of cells with short telomeres correlated positively with serum C-reactive protein level, which reflects inflammation. p53 expression was increased in mononuclear cells from hemodialysis patients. Mononuclear cells from hemodialysis patients with decreased telomere length mainly showed the CD14dim/CD16bright phenotype; conversely, cells with normal telomeres presented the CD14bright/CD16dim phenotype. Finally, mononuclear cells from hemodialysis patients, but not controls, spontaneously produced the proinflammatory cytokines IL-1 beta and IL-6. Conclusion: This study shows the presence of a prematurely senescent subpopulation of peripheral mononuclear cells in hemodialysis patients. These senescent cells probably result from repeated activation and may have a pathophysiological role in the chronic inflammation described in hemodialysis patients.