Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study

Exacerbation of oxidative stress during sickle vaso-occlusive crisis is associated with decreased anti-band 3 autoantibodies rate and increased red blood cell-derived microparticle level: a prospective study
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DOI:
10.1111/bjh.14476
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发表时间:
2017-03-01
影响因子:
6.5
通讯作者:
Hardy-Dessources, Marie-Dominique
Hardy-Dessources, Marie-Dominique
中科院分区:
医学2区
文献类型:
--
作者:
Hierso, Regine;Lemonne, Nathalie;Hardy-Dessources, Marie-Dominique

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痛苦的血管闭塞危象是镰状细胞性贫血的一个标志,是由复杂的、不完全了解的机制引起的。持续的内源性和外源性氧化应激引起的红细胞(RBC)损伤可能会促进血管闭塞危象的发生。为了深入了解氧化应激在血管闭塞危象发生中的相关性,我们前瞻性地比较了 32 名镰状细胞性贫血成人在血管闭塞危象和稳态条件下各种氧化标记物的表达水平。与稳态条件相比,在血管闭塞危机期间,血浆中游离血红素、高级氧化蛋白产物和髓过氧化物酶、红细胞 caspase-3 活性以及总微粒、中性粒细胞和红细胞衍生微粒的浓度均升高,而红细胞中还原型谷胱甘肽含量降低。此外,天然抗带3自身抗体水平在危机期间下降,并与血浆高级氧化蛋白产物和红细胞caspase-3活性的升高呈负相关。这些数据显示镰状细胞性贫血患者血管闭塞危机期间氧化应激加剧,并强烈表明有害循环红细胞衍生微粒浓度较高和抗带3自身抗体水平降低可能都与氧化带3募集到膜聚集体有关。
Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.