Genome Research Center for Allergy and Respiratory disease, Soonchunhyang University Hospital, Bucheon, Gyeonggi-do, Republic of Korea.
Am J Respir Crit Care Med. 2011 Sep 1;184(5):528-36. doi: 10.1164/rccm.201006-0951OC.
Airway inflammation and remodeling during asthma are attributed to the altered expression of biologically relevant proteins.
To search for asthma-specific proteins in bronchoalveolar lavage fluid (BAL) from individuals with asthma and to validate the identified proteins in an experimental model of asthma.
Liquid chromatography-tandem mass spectrometry was performed to identify proteins in BAL fluid found by two dimensional electrophoresis (2DE) to be differentially expressed in subjects with asthma versus control subjects. Group-specific component (Gc) and mRNA levels were measured using an ELISA, Western blots, and PCR. A neutralization study using an antibody against Gc protein was performed in an experimental asthma model.
Based on 2DE, 15 proteins were significantly up-regulated or down-regulated in eight subjects with asthma compared with eight control subjects. The protein levels of Gc, hemopexin, and haptoglobin-b were increased, whereas the a1- antitrypsin and glutathione S-transferase levels were decreased in subjects with asthma. The Gc concentration in BAL fluid was significantly elevated in 67 subjects with asthma compared with that in 22 control subjects (P < 0.009). The Gc was significantly correlated with the neutrophil percentage in BAL fluid of subjects with asthma (P = 0.001). Gc mRNA and protein levels were higher in ovalbumin-sensitized/ challenged asthma mice than in sham-treated mice. Gc protein were expressed on alveolar macrophages and on epithelial cells. Treatment with an anti-Gc antibody dose-dependently reduced the ovalbumin sensitization/challenge-induced enhancement of airway hyperreactivity, airway inflammation, goblet cell hyperplasia,and levels of eotaxin, interleukin-4, -5, and -13, and interferon-g.
Gc may be involved in the development of asthma, and the neutralization of Gc protein could be a therapeutic strategy for asthma.
哮喘时气道炎症和重塑归因于生物学相关蛋白表达的改变。
在哮喘患者的支气管肺泡灌洗液（BAL）中寻找哮喘特异性蛋白，并在哮喘的实验模型中验证鉴定的蛋白。
采用液相色谱-串联质谱法对二维电泳（2DE）发现的 BAL 液中差异表达的蛋白进行鉴定。采用 ELISA、Western blot 和 PCR 检测组特异性成分（Gc）和 mRNA 水平。在哮喘实验模型中进行针对 Gc 蛋白的中和研究。
基于 2DE，与 8 名对照受试者相比，8 名哮喘患者有 15 种蛋白表达显著上调或下调。Gc、血红素结合蛋白和触珠蛋白-b 的蛋白水平升高，而 a1-抗胰蛋白酶和谷胱甘肽 S-转移酶的水平降低。67 例哮喘患者 BAL 液中的 Gc 浓度明显高于 22 例对照受试者（P <0.009）。哮喘患者 BAL 液中的 Gc 与中性粒细胞百分比呈显著正相关（P =0.001）。卵清蛋白致敏/激发哮喘小鼠的 Gc mRNA 和蛋白水平均高于假处理小鼠。Gc 蛋白表达于肺泡巨噬细胞和上皮细胞上。用抗 Gc 抗体进行治疗可剂量依赖性地降低卵清蛋白致敏/激发诱导的气道高反应性、气道炎症、杯状细胞增生以及嗜酸性粒细胞趋化因子、白细胞介素-4、-5 和-13、干扰素-g 的水平。
Gc 可能参与哮喘的发生，中和 Gc 蛋白可能是治疗哮喘的一种策略。
