Lilly C M, Nakamura H, Belostotsky O I, Haley K J, Garcia-Zepeda E A, Luster A D, Israel E
Combined Program in Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Am J Respir Crit Care Med. 2001 Jun;163(7):1669-75. doi: 10.1164/ajrccm.163.7.9812044.
Expression of pulmonary eotaxin protein and mRNA was determined in six subjects with atopic asthma and five nonatopic normal subjects. Levels of eotaxin expression and eosinophil mobilization were compared before and after segmental allergen challenge in subjects with atopic asthma. In the absence of allergen challenge, we found significantly higher levels of eotaxin in the bronchoalveolar lavage (BAL) fluid of subjects with asthma than in that of normal subjects (25 +/- 3 versus 15 +/- 2 pg/ml, p < 0.05). BAL eotaxin levels increased after segmental allergen challenge in all six subjects with atopic asthma tested, with a mean increase from 22 +/- 4 to 53 +/- 10 pg/ml (p = 0.013). Segmental allergen challenge was associated with a significant increase in the percentage of BAL macrophages and eosinophils that were immunopositive for eotaxin. Eotaxin mRNA was detectable by northern analysis in BAL cells exclusively from allergen-challenged segments. Allergen- induced increases in eotaxin levels were strongly associated with increases in BAL eosinophil recovery (r(2) = 0.88, p = 0.0036). Segmental allergen challenge also increased eotaxin expression in airway epithelial and endothelial cells obtained by endobronchial biopsy. These findings demonstrate, for the first time, that the airways of subjects with allergic asthma respond to allergen by increasing eotaxin expression. The tissue loci of eotaxin expression, the levels of eotaxin recovered in BAL fluid, and the association of eotaxin levels with eosinophil mobilization suggest either that eotaxin plays a mechanistic role in allergen-induced airway eosinophilia or that it serves as a biomarker for the causal mechanisms.
在6名特应性哮喘患者和5名非特应性正常受试者中测定了肺嗜酸性粒细胞趋化因子蛋白和mRNA的表达。比较了特应性哮喘患者在节段性变应原激发前后嗜酸性粒细胞趋化因子的表达水平和嗜酸性粒细胞动员情况。在没有变应原激发的情况下，我们发现哮喘患者支气管肺泡灌洗（BAL）液中嗜酸性粒细胞趋化因子的水平显著高于正常受试者（25±3对15±2 pg/ml，p<0.05）。在所有6名接受测试的特应性哮喘患者中，节段性变应原激发后BAL嗜酸性粒细胞趋化因子水平升高，平均从22±4 pg/ml增至53±10 pg/ml（p = 0.013）。节段性变应原激发与BAL巨噬细胞和嗜酸性粒细胞中嗜酸性粒细胞趋化因子免疫阳性百分比的显著增加相关。通过Northern分析仅在变应原激发节段的BAL细胞中可检测到嗜酸性粒细胞趋化因子mRNA。变应原诱导的嗜酸性粒细胞趋化因子水平升高与BAL嗜酸性粒细胞回收率增加密切相关（r² = 0.88，p = 0.0036）。节段性变应原激发还增加了通过支气管活检获得的气道上皮细胞和内皮细胞中嗜酸性粒细胞趋化因子的表达。这些发现首次证明，过敏性哮喘患者的气道通过增加嗜酸性粒细胞趋化因子的表达对变应原作出反应。嗜酸性粒细胞趋化因子表达的组织位点、BAL液中回收的嗜酸性粒细胞趋化因子水平以及嗜酸性粒细胞趋化因子水平与嗜酸性粒细胞动员的关联表明，嗜酸性粒细胞趋化因子要么在变应原诱导的气道嗜酸性粒细胞增多中起机制性作用，要么作为因果机制的生物标志物。
