过敏性支气管哮喘小鼠气道中的ADAM8上调
2009/06/26
近期的生物芯片分析显示，解聚素和金属蛋白酶（ADAM）8（ADAM8；也称为CD156）是哮喘的候选基因之一。然而，目前对ADAM8的功能及其在气道中的定位了解甚少。本实验在小鼠过敏性支气管哮喘模型中研究ADAM8在气道的定位及其表达变化。对雄性BALB/c 小鼠采用卵清蛋白抗原反复刺激，诱导哮喘反应。模型建立后，采用定量RT-PCR和免疫组织化学法分别检测ADAM8的mRNA及其蛋白表达。与对照小鼠相比，哮喘模型ADAM8 mRNA显著增加。免疫组织化学检测显示，ADAM8主要位于气道上皮、气道平滑肌和肺实质浸润细胞（主要为巨噬细胞）。与致敏的对照动物相比，免疫染色检测到气道上述细胞都有不同程度的ADAM8高表达。气道ADAM8的上调可能参与了气道炎症或/和气道高反应性的致病过程，后两者是支气管哮喘的主要特征。
（陈欣 审校）
Chiba Y,et al. Lung. 2009 Apr 17. [Epub ahead of print]
Upregulation of ADAM8 in the Airways of Mice with Allergic Bronchial Asthma.
Recent microarray analyses revealed that a disintegrin and metalloproteinase (ADAM) 8 (ADAM8; also called CD156) is one of the asthma candidate genes. However, the function of ADAM8 and its localization in the airways are still poorly understood. In the present study, the changes in the expression and localization of ADAM8 in the airways of a mouse model of allergic bronchial asthma were investigated. Male BALB/c mice were sensitized and repeatedly challenged with ovalbumin antigen to induce asthmatic response. After the final antigen challenge, mRNA and protein expressions of ADAM8 were elucidated by quantitative RT-PCR and immunohistochemistry. The mRNA expression of ADAM8 in the airways was significantly increased in this animal model of asthma compared with naive animals. Immunohistochemical examinations revealed that ADAM8 was located in airway epithelia, airway smooth muscles, and infiltrated cells (mainly macrophages) into lung parenchyma. A distinctly stronger immunostaining of ADAM8 was observed in these airway cells of the repeatedly antigen-challenged mice compared with those of the sensitized control animals. An upregulation of ADAM8 in the airways might be involved in the pathogenesis of airway inflammation and/or hyperresponsiveness, characteristic features of allergic bronchial asthma.
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