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Molecular biologic approach for clarification of the role of bronchial epithelial cells for development of asthma

阐明支气管上皮细胞在哮喘发展中的作用的分子生物学方法

基本信息

批准号：
08670679
负责人：
OHTA Ken
金额：
$ 1.22万
依托单位：
Teikyo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

It has been known that allergic inflammation at the airway and associated disorder of airway epithelial cells play important roles as causative factors for the airway hyperresponsiveness. In the study, we have studied cytokine production of bronchial epithelial cells in vitro and the effects of these cytokine in vivo to analyze mechanism of relationship between allergic inflammation and airway hyperresponsiveness. We used BEAS-2B cells, a cell line of bronchial epithelial cells transformed by adenovirus-12/SV-40 hybrid and cultured in F-12 medium. SIgA and anti IgA complex induced the release of GM-CSF and IL-8 in a dose-dependent manner. The existence of IgA receptor was demonstrated by flow cytometry analysis using anti-IgA receptor specific monoclonal antibodies. Next, we have established mice asthmatic model sensitized in ovalbumin specific manner and tried to clarify the effects of GM-CSF in vivo. A/J mice were first immunized with OA+Alum, following intranasal sensitization with QA.Intranasal sensitization with OA increased the airway responsiveness to acetylcholine. A pathological study revealed that the treatment with OA replaced the ciliated epithelial cells of the airways with Clara cells. The transnasal administration of GM-CSF neutralizing antibody completely inhibited the increase of airway hyperresponsiveness caused by OA.In conclusion, GM-CSF, which can be produced by bronchial epithelial cells, plays an important role in enhancing airway responsiveness at the site of the airway.

已知气道变态反应性炎症及其相关的气道上皮细胞紊乱是导致气道高反应性的重要因素。在本研究中，我们研究了体外培养的支气管上皮细胞产生的细胞因子以及这些细胞因子在体内的作用，以分析过敏性炎症与气道高反应性之间的关系的机制。我们用腺病毒-12/SV-40杂交瘤细胞转化的BEAS-2B细胞，在F-12培养液中培养。SIgA和抗IgA复合体以剂量依赖的方式诱导GM-CSF和IL-8的释放。用抗IgA受体的特异性单抗进行流式细胞术分析，证实了IgA受体的存在。接下来，我们建立了卵蛋白特异性致敏的小鼠哮喘模型，并试图阐明GM-CSF在体内的作用。A/J小鼠首先用OA+明矾免疫，然后用QA鼻腔致敏，鼻腔致敏增加了对乙酰胆碱的气道反应性。一项病理学研究显示，OA治疗用Clara细胞取代了呼吸道的纤毛上皮细胞。经鼻给予GM-CSF中和抗体可完全抑制OA引起的气道高反应性增加。结论：GM-CSF可由支气管上皮细胞产生，在增强气道部位的气道高反应性中起重要作用。