Powell N, Humbert M, Durham S R, Assoufi B, Kay A B, Corrigan C J
National Heart & Lung Institute at Imperial College of Science, Technology & Medicine, London, UK.
Eur Respir J. 1996 Dec;9(12):2454-60. doi: 10.1183/09031936.96.09122454.
The selective recruitment of eosinophils into the mucosal lining of the airways is a prominent feature of atopic asthma, and is believed to be an important component in the disease pathogenesis. The precise stimuli responsible for the influx of eosinophils remain unclear. Using a semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) technique, the numbers of copies (relative to the "housekeeping" gene beta-actin) of messenger ribonucleic acid (mRNA) encoding the eosinophil-active chemotactic cytokines, the factor regulated upon activation in normal T-cells expressed and secreted (RANTES) and monocyte chemotactic protein-3 (MCP-3), was measured in bronchial biopsies from atopic asthmatic patients (n = 9), and compared with atopic nonasthmatic (n = 8) and nonatopic nonasthmatic (n = 8) control subjects. In addition, further biopsies from each subject were prepared for immunohistochemistry and the numbers of activated (EG2+) eosinophils measured. The expression of RANTES mRNA was significantly elevated in the atopic asthmatic group as compared to the atopic nonasthmatic controls (p = 0.013) and the nonatopic nonasthmatic controls (p = 0.007). Similarly, the expression of mRNA encoding MCP-3 was significantly elevated in the atopic asthmatic group, relative to the atopic nonasthmatic controls (p = 0.014) and the nonatopic nonasthmatic control group (p = 0.011). Elevated RANTES and MCP-3 mRNA expression was associated with significantly increased numbers of bronchial mucosal eosinophils in the atopic asthmatic patients as compared to the atopic nonasthmatic (p = 0.03) and nonatopic nonasthmatic (p = 0.006) control subjects. In conclusion, we have identified elevated expression of messenger ribonucleic acid encoding RANTES and monocyte chemotactic protein-3 in the bronchial mucosa of atopic asthmatic patients relative to controls. These findings are compatible with the hypothesis that eosinophil-active beta-chemokines play a role in the mechanism of eosinophil recruitment to the asthmatic bronchial mucosa.
嗜酸性粒细胞选择性募集至气道黏膜层是特应性哮喘的一个显著特征，并且被认为是该疾病发病机制中的一个重要组成部分。导致嗜酸性粒细胞流入的精确刺激因素仍不清楚。使用半定量逆转录聚合酶链反应（RT-PCR）技术，在特应性哮喘患者（n = 9）的支气管活检组织中测量编码嗜酸性粒细胞活性趋化细胞因子、正常T细胞激活后表达和分泌的调节因子（RANTES）以及单核细胞趋化蛋白-3（MCP-3）的信使核糖核酸（mRNA）的拷贝数（相对于“管家”基因β-肌动蛋白），并与特应性非哮喘患者（n = 8）和非特应性非哮喘患者（n = 8）对照进行比较。此外，为免疫组织化学准备了每个受试者的更多活检组织，并测量活化（EG2 +）嗜酸性粒细胞的数量。与特应性非哮喘对照组（p = 0.013）和非特应性非哮喘对照组（p = 0.007）相比，特应性哮喘组中RANTES mRNA的表达显著升高。同样，相对于特应性非哮喘对照组（p = 0.014）和非特应性非哮喘对照组（p = 0.011），特应性哮喘组中编码MCP-3的mRNA表达显著升高。与特应性非哮喘（p = 0.03）和非特应性非哮喘（p = 0.006）对照受试者相比，特应性哮喘患者中RANTES和MCP-3 mRNA表达升高与支气管黏膜嗜酸性粒细胞数量显著增加相关。总之，我们已经确定相对于对照组，特应性哮喘患者支气管黏膜中编码RANTES和单核细胞趋化蛋白-3的信使核糖核酸表达升高。这些发现与嗜酸性粒细胞活性β趋化因子在嗜酸性粒细胞募集至哮喘支气管黏膜机制中起作用的假设相符。
