Study on cell-to-cell interactions between airway epithelial cells and inflammatory cells in the pathogenesis of asthma

支气管哮喘的特征是严重的支气管收缩和持续的气道炎症，并伴有高反应性。嗜酸性粒细胞、肥大细胞和淋巴细胞在支气管哮喘的发病机制中起重要作用。我们研究了细胞间的相互作用，特别是气道上皮细胞和炎症细胞之间的体外。气道上皮细胞来源的纤连蛋白、IL-8和RANTES分别对肥大细胞、淋巴细胞和嗜酸性粒细胞具有趋化活性。气道上皮细胞也表达和释放IL-6和GM-CSF，激活淋巴细胞和嗜酸性粒细胞，上皮来源的内皮素-l对气道平滑肌显示出强有力的支气管收缩作用。我们进一步表明，嗜酸性粒细胞与支气管上皮细胞的粘附是嗜酸性粒细胞活化和脱颗粒的重要信号之一。气道上皮细胞的生长和分化是气道粘膜修复过程的关键步骤，并且正确修复的失败可能导致组织重塑。我们发现嗜酸性粒细胞和上皮细胞都表达TGF β，这可能是抑制气道正常修复和诱导气道重塑的一个因素。我们相信，我们的发现为哮喘的发生提供了细胞间相互作用的新见解，并可能有助于开发更好的治疗这种疾病的策略。

Bronchial asthma is characterized by profound bronchoconstriction and persistent airway inflammation associated with hyperresponsiveness. There is a dense accumulation of eosinophils, mast cells and lymphocytes, whcih are belived to play important roles in the pathogenesis of asthma. We investigated the cell-to-cell interactions, especially between airway epithelial cells and the inflammatory cells in vitro. Airway epithelial cell-derived fibronectin, IL-8 and RANTES showed a chemotactic activity for mast cells, Iymphocytes and eosinophils, respectively. Airway epithelial cells also express and release IL-6 and GM-CSF which activate lymphocytes and eosinophils, and epithelium-derived endothelin-lshowed a potent bronchoconstricting action on airway smooth muscles.We further showed that eosinophil adhesion to bronchial epithelial cells is one of the important signals for eosinophil activation and degranulation.Airway epithelial cell growth and differentiation are crucial steps for the repair processes of airway mucosa, and failure of correct repair may result in tissue remodeling. We demonstrated that both eosinophils and epithelial cells express TGFbeta, whcih may be a factor to suppress normal repair and to induce remodeling in the airways. We believe our findings gave new insights into the cell-to-cell interactions important in the thogenesis of asthma, and may help develop better strategies for the treatment of this disease.