Peltoniemi Mirva J, Rytilä Paula H, Harju Terttu H, Soini Ylermi M, Salmenkivi Kaisa M, Ruddock Lloyd W, Kinnula Vuokko L
Biocenter Oulu and Department of Biochemistry, University of Oulu, Oulu, Finland.
Respir Res. 2006 Oct 25;7(1):133. doi: 10.1186/1465-9921-7-133.
One typical feature in chronic obstructive pulmonary disease (COPD) is the disturbance of the oxidant/antioxidant balance. Glutaredoxins (Grx) are thiol disulfide oxido-reductases with antioxidant capacity and catalytic functions closely associated with glutathione, the major small molecular weight antioxidant of human lung. However, the role of Grxs in smoking related diseases is unclear.
Immunohistochemical and Western blot analyses were conducted with lung specimens (n = 45 and n = 32, respectively) and induced sputum (n = 50) of healthy non-smokers and smokers without COPD and at different stages of COPD.
Grx1 was expressed mainly in alveolar macrophages. The percentage of Grx1 positive macrophages was significantly lower in GOLD stage IV COPD than in healthy smokers (p = 0.021) and the level of Grx1 in total lung homogenate decreased both in stage I-II (p = 0.045) and stage IV COPD (p = 0.022). The percentage of Grx1 positive macrophages correlated with the lung function parameters (FEV1, r = 0.45, p = 0.008; FEV1%, r = 0.46, p = 0.007, FEV/FVC%, r = 0.55, p = 0.001). Grx1 could also be detected in sputum supernatants, the levels being increased in the supernatants from acute exacerbations of COPD compared to non-smokers (p = 0.013) and smokers (p = 0.051).
The present cross-sectional study showed that Grx1 was expressed mainly in alveolar macrophages, the levels being decreased in COPD patients. In addition, the results also demonstrated the presence of Grx1 in extracellular fluids including sputum supernatants. Overall, the present study suggests that Grx1 is a potential redox modulatory protein regulating the intracellular as well as extracellular homeostasis of glutathionylated proteins and GSH in human lung.
慢性阻塞性肺疾病（COPD）的一个典型特征是氧化/抗氧化平衡紊乱。谷氧还蛋白（Grx）是一类硫醇二硫化物氧化还原酶，具有抗氧化能力，其催化功能与谷胱甘肽密切相关，谷胱甘肽是人类肺组织中主要的小分子抗氧化剂。然而，Grx在吸烟相关疾病中的作用尚不清楚。
对健康非吸烟者、无COPD的吸烟者以及处于不同COPD阶段的吸烟者的肺组织标本（分别为n = 45和n = 32）和诱导痰（n = 50）进行免疫组织化学和蛋白质印迹分析。
Grx1主要在肺泡巨噬细胞中表达。在GOLD IV期COPD患者中，Grx1阳性巨噬细胞的百分比显著低于健康吸烟者（p = 0.021），并且在I-II期（p = 0.045）和IV期COPD患者（p = 0.022）中，全肺匀浆中Grx1的水平均降低。Grx1阳性巨噬细胞的百分比与肺功能参数相关（FEV1，r = 0.45，p = 0.008；FEV1%，r = 0.46，p = 0.007，FEV/FVC%，r = 0.55，p = 0.001）。在痰液上清液中也可检测到Grx1，与非吸烟者（p = 0.013）和吸烟者（p = 0.051）相比，COPD急性加重期患者痰液上清液中Grx1的水平升高。
本横断面研究表明，Grx1主要在肺泡巨噬细胞中表达，在COPD患者中其水平降低。此外，结果还证明了在包括痰液上清液在内的细胞外液中存在Grx1。总体而言，本研究表明Grx1是一种潜在的氧化还原调节蛋白，可调节人肺组织中谷胱甘肽化蛋白和谷胱甘肽的细胞内及细胞外稳态。
