Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein.
Inflammation in Sickle Cell Disease: Differential and Down-Expressed Plasma Levels of Annexin A1 Protein.
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DOI：
10.1371/journal.pone.0165833
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Bonini-Domingos CR
中科院分区：
文献类型：
--
作者：
Torres LS;Okumura JV;Silva DG;Mimura KK;Belini-Júnior É;Oliveira RG;Lobo CL;Oliani SM;Bonini-Domingos CR
镰状细胞病（SCD）是一种遗传性溶血性贫血，其病理生理学是由血红蛋白S（Hb S）聚合驱动的，导致溶血和血管闭塞事件。炎症是这些过程的基本组成部分，持续的炎症刺激可导致组织损伤。因此，促消退途径出现，以恢复体内平衡。例如，存在膜联蛋白A1（ANXA 1），其是参与减少嗜中性粒细胞-内皮相互作用、加速中性粒细胞凋亡和刺激巨噬细胞吞噬细胞增多的内源性抗炎蛋白。我们研究了SCD患者血浆中ANXA 1的表达及其与贫血、溶血和炎症参数的关系。三个SCD基因型被认为是：纯合子遗传的血红蛋白S（Hb SS）和血红蛋白S之间的关联和血红蛋白变体D-旁遮普（Hb SD）和C（Hb SC）。通过ELISA定量SCD患者和无血红蛋白病的对照个体血浆中的ANXA 1和促炎细胞因子。采用流式细胞仪和分光光度计分析血液学和生化指标。与对照组相比，SCD患者的ANXA 1血浆水平约低三倍，并且在SCD基因型中，Hb SS个体的ANXA 1水平升高最多（约高三倍）。SCD组的促炎细胞因子高于对照组。贫血和溶血标记物在Hb SS和Hb SD基因型中高于Hb SC患者。Hb SS基因型患者的白色细胞数和血小板数均较高，且与ANXA 1水平呈正相关。我们发现ANXA 1在SCD基因型中下调并差异表达。其表达似乎取决于病变的炎症、溶血和血管闭塞特征。这些数据可能会导致新的生物学靶点的治疗干预SCD。
Sickle cell disease (SCD) is an inherited hemolytic anemia whose pathophysiology is driven by polymerization of the hemoglobin S (Hb S), leading to hemolysis and vaso-occlusive events. Inflammation is a fundamental component in these processes and a continuous inflammatory stimulus can lead to tissue damages. Thus, pro-resolving pathways emerge in order to restore the homeostasis. For example there is the annexin A1 (ANXA1), an endogenous anti-inflammatory protein involved in reducing neutrophil-endothelial interactions, accelerating neutrophil apoptosis and stimulating macrophage efferocytosis. We investigated the expression of ANXA1 in plasma of SCD patients and its relation with anemic, hemolytic and inflammatory parameters of the disease. Three SCD genotypes were considered: the homozygous inheritance for Hb S (Hb SS) and the association between Hb S and the hemoglobin variants D-Punjab (Hb SD) and C (Hb SC). ANXA1 and proinflammatory cytokines were quantified by ELISA in plasma of SCD patients and control individuals without hemoglobinopathies. Hematological and biochemical parameters were analyzed by flow cytometry and spectrophotometer. The plasma levels of ANXA1 were about three-fold lesser in SCD patients compared to the control group, and within the SCD genotypes the most elevated levels were found in Hb SS individuals (approximately three-fold higher). Proinflammatory cytokines were higher in SCD groups than in the control individuals. Anemic and hemolytic markers were higher in Hb SS and Hb SD genotypes compared to Hb SC patients. White blood cells and platelets count were higher in Hb SS genotype and were positively correlated to ANXA1 levels. We found that ANXA1 is down-regulated and differentially expressed within the SCD genotypes. Its expression seems to depend on the inflammatory, hemolytic and vaso-occlusive characteristics of the diseased. These data may lead to new biological targets for therapeutic intervention in SCD.
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影响因子：
4.8
作者：
La, M;D'Amico, M;Perretti, M
通讯作者：
Perretti, M
影响因子：
5.5
作者：
Lanaro, C.;Franco-Penteado, C. F.;Costa, F. F.
通讯作者：
Costa, F. F.
DOI：
10.1001/archpedi.1993.02160350071011
发表时间：
1993-11-01
影响因子：
--
作者：
POWARS, D;HITI, A
通讯作者：
HITI, A
影响因子：
2.4
作者：
Hoppe, Carolyn C.
通讯作者：
Hoppe, Carolyn C.
影响因子：
2.4
作者：
Hebbel, Robert P.
通讯作者：
Hebbel, Robert P.