Integrin expression and H2O2 production in circulating and splenic leukocytes of obese rats.

Integrin expression and H2O2 production in circulating and splenic leukocytes of obese rats.
复制标题

肥胖大鼠循环和脾白细胞中整合素的表达和 H2O2 的产生。

DOI:
10.1038/oby.2007.262
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发表时间:
2007
期刊:
Obesity (Silver Spring, Md.)
影响因子:
--
通讯作者:
Rodriguez-Iturbe,Bernardo
Rodriguez-Iturbe,Bernardo
中科院分区:
--
文献类型:
--
作者:
Kim,ChoongH;Vaziri,NosratolaD;Rodriguez-Iturbe,Bernardo

文献摘要

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目的:肥胖与氧化应激和炎症有关。我们假设肥胖的促炎状态可能导致自发激活,从而增加循环白细胞中活性氧(ROS)的产生和整合素的表达。方法:采用流式细胞术检测24周龄雄性肥胖、血压正常但未患糖尿病的Zucker大鼠(n= 6)和瘦肉大鼠(n= 6)外周血和脾白细胞中整合素的表达(免疫染色)以及超氧化物和过氧化氢的产生(荧光探针)。结果:肥胖大鼠有高脂血症,动脉压、血糖、肌酐浓度正常。然而,肥胖大鼠表现出循环和脾CD4+和CD8+ T淋巴细胞以及脾巨噬细胞产生过氧化氢的增加。与此同时,外周血和脾CD4+ T细胞中的CD11a、循环巨噬细胞中的CD11b、循环粒细胞中的CD11a和CD18表达上调。结论:本研究为肥胖Zucker大鼠在糖尿病或高血压发生前外周血白细胞自发活化、T淋巴细胞和单核细胞ROS生成增加提供了直接证据。这些发现说明了肥胖、氧化应激和炎症之间的联系。
Objective:Obesity is associated with oxidative stress and inflammation. We hypothesized that the pro‐inflammatory state in obesity may result in spontaneous activation and, hence, increased generation of reactive oxygen species (ROS) and integrin expression in the circulating leukocytes.Methods:Flow cytometry was used to determine integrin expression (immunostaining) as well as superoxide and hydrogen peroxide productions (fluorescent probes) in the peripheral blood and splenic leukocyte of 24‐week‐old male obese normotensive and not‐as‐yet diabetic Zucker rats (n= 6) and their lean counterparts (n= 6).Results:Obese rats had hyperlipidemia and normal arterial pressure, plasma glucose, and creatinine concentrations. Nevertheless, obese rats exhibited increased hydrogen peroxide production by circulating and splenic CD4+ and CD8+ T lymphocytes and by splenic macrophages. This was accompanied by up‐regulations of CD11a expression in the peripheral blood and splenic CD4+ T cells, CD11b in circulating macrophages, and CD11a and CD18 in circulating granulocytes.Conclusion:The study revealed direct evidence of spontaneous leukocyte activation and increased ROS generation by T lymphocytes and monocytes in the peripheral blood of obese Zucker rats before the development of diabetes or hypertension. These findings illustrate the link between obesity, oxidative stress, and inflammation.