不同哮喘表型中性粒细胞基因表达和细胞因子合成的差异
2010/08/20
关键词：气道炎症；哮喘表型；基因表达；自然免疫；IL-8；中性粒细胞
根据气道内炎症细胞的类型，哮喘可分为嗜酸性粒细胞增多和非嗜酸性粒细胞增多两种表型。中性粒细胞在自然免疫中发挥重要的作用，并在非嗜酸性粒细胞性哮喘中增多。为了评价在中性粒细胞在不同表型的哮喘中的活性，Baines等进行的一项小样本对照研究。
研究对象包括8例嗜酸性粒细胞增多的哮喘患者、9例非嗜酸性粒细胞增多患者和11健康对照者。收集研究对象的诱导痰和血标本。分离并体外培养中性粒细胞。ElISA法测定细胞因子，基因芯片和定量PCR方法测定基因表达。
研究结果显示，非嗜酸性粒细胞增多性哮喘，血中性粒细胞IL-8释放水平更高。但在不同表型间，细胞因子的基因表达和痰中性粒细胞蛋白的合成并无差异。基因芯片分析显示，非嗜酸性粒细胞增多性哮喘患者的密切相关基因图与嗜酸性粒细胞增多性哮喘患者的明显不同。两组患者间有317个基因存在明显不同，这些基因主要与细胞迁移和调控凋亡有关。
本研究发现非嗜酸性粒细胞性哮喘和嗜酸性粒细胞性哮喘与独特的基因图明显相关。研究结果在整体水平为不同表型哮喘所涉及的分子机制提供了新的证据。非嗜酸性粒细胞性哮喘的机制可能与血中性粒细胞趋化和幸存有关。
（韩伟 青岛大学附属青岛市立医院东院 266071 摘译）
（Eur Respir J 2010; 35:522-531）
（Eur Respir J 2010; 35:522-531）
Differential gene expression and cytokine production from neutrophils in asthma phenotypes
K. J. Baines1,2, J. L. Simpson1,2, N. A. Bowden3, R. J. Scott3 and P. G. Gibson1,2
Keywords: Airway inflammation, asthma phenotypes, gene expression, innate immunity, interleukin-8, neutrophils
Asthma is characterised into eosinophilic and non-eosinophilic phenotypes based on inflammatory cell patterns in airway secretions. Neutrophils are important in innate immunity, and are increased in the airways in non-eosinophilic asthma. The present study investigated the activity of neutrophils in asthma phenotypes.
Participants with eosinophilic (n = 8) and non-eosinophilic asthma (n = 9) and healthy controls (n = 11) underwent sputum induction and blood collection. Neutrophils were isolated and cultured with or without lipopolysaccharide. Cytokines were measured by ELISA, and gene expression was analysed using a gene expression microarray and quantitative PCR.
In non-eosinophilic asthma, blood neutrophils released significantly higher levels of interleukin-8 at rest. Cytokine gene expression and sputum neutrophil protein production did not differ between asthma subtypes. Microarrays demonstrated closely related expression profiles from participants with non-eosinophilic asthma that were significantly distinct from those in eosinophilic asthma. A total of 317 genes were significantly altered in resting neutrophils from participants with non-eosinophilic asthma versus eosinophilic asthma, including genes related to cell motility and regulation of apoptosis.
Non-eosinophilic and eosinophilic asthma are associated with specific gene expression profiles, providing further evidence that these phenotypes of asthma involve different molecular mechanisms of disease pathogenesis at the systemic level. The mechanisms of non-eosinophilic asthma may involve enhancement of blood neutrophil chemotaxis and survival.
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有氧训练逆转哮喘模型小鼠的气道炎症和气道重构
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重症哮喘时p38 MAPK对激素抑制细胞因子释放的抑制作用
