Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure.
Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure.
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发表时间：
1998-09
影响因子：
4.4
通讯作者：
V. Witko-Sarsat;M. Friedlander;T. N. Khoa;C. Capeillère-Blandin;A. Nguyen;S. Canteloup;J. Dayer
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文献类型：
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作者：
V. Witko-Sarsat;M. Friedlander;T. N. Khoa;C. Capeillère-Blandin;A. Nguyen;S. Canteloup;J. Dayer
我们先前证实了晚期氧化蛋白产物（AOPP）的存在，这是接受维持性透析的尿毒症患者血浆中氧化应激的一种新标志物。本研究在162例尿毒症患者中进行，结果显示AOPP的血浆浓度随着慢性肾功能衰竭的进展而增加，并与晚期糖基化终末产物（AGE）-戊糖苷密切相关（r = 0.52，p < 0.001）。在体内，AOPP和AGE-戊糖苷与尿毒症相关的单核细胞介导的炎性综合征的相关性通过AOPP或AGE-戊糖苷与单核细胞活化标志物（包括新蝶呤、IL-1 R拮抗剂、TNF-α和TNF可溶性受体（TNF-sR 55和TNF-sR75））之间的密切相关性得到证明。为了确定AOPP和AGE直接参与单核细胞活化的机制，分别用氧化剂或葡萄糖处理人血清白蛋白（HSA），在体外产生AOPP-HSA和AGE-HSA。光谱分析证实AOPP-HSA含有羰基和二酪氨酸。AOPP-HSA和AGE-HSA，但不是纯化的二酪氨酸，能够触发人单核细胞在培养物中的氧化爆发。AOPP-HSA诱导的呼吸爆发依赖于氧化剂的氯化性质和HSA/HOCI的摩尔比。总的来说，这些数据首先证明AOPP作为氧化应激和单核细胞呼吸爆发的介导物，这表明单核细胞在与慢性尿毒症相关的免疫失调中既是靶又是作用者。
We previously demonstrated the presence of advanced oxidation protein products (AOPP), a novel marker of oxidative stress in the plasma of uremic patients receiving maintenance dialysis. The present study in a cohort of 162 uremic patients showed that plasma concentrations of AOPP increased with progression of chronic renal failure and were closely related to advanced glycation end products (AGE)-pentosidine (r = 0.52, p < 0.001), taken as a marker of AGE. In vivo, the relevance of AOPP and AGE-pentosidine in monocyte-mediated inflammatory syndrome associated with uremia was evidenced by close correlations between AOPP or AGE-pentosidine and monocyte activation markers, including neopterin, IL-1R antagonist, TNF-alpha, and TNF soluble receptors (TNF-sR55 and TNF-sR75). To determine the mechanisms by which AOPP and AGE could be directly involved in monocyte activation, AOPP-human serum albumin (HSA) and AGE-HSA were produced in vitro by treating HSA with oxidants or glucose, respectively. Spectroscopic analysis confirmed that AOPP-HSA contains carbonyls and dityrosine. Both AOPP-HSA and AGE-HSA, but not purified dityrosine, were capable of triggering the oxidative burst of human monocytes in cultures. The AOPP-HSA-induced respiratory burst was dependent on the chlorinated nature of the oxidant and on the molar ratio HSA/HOCI. Collectively, these data first demonstrate that AOPP act as a mediator of oxidative stress and monocyte respiratory burst, which points to monocytes as both target and actor in the immune dysregulation associated with chronic uremia.