AIRWAY MORPHOLOGY IN IL 11 OVEREXPRESSION TRANSGENIC MICE

支气管哮喘的特征是气道慢性化 炎症 体内和体外研究表明， 哮喘气道中多种细胞因子的失调。 然而，在大多数情况下，单个细胞因子的能力， 介导的病理和生理紊乱的特点， 对这种疾病了解甚少。 为了解决这个问题，我们必须 开发了一个系统，使我们能够在小鼠中表达细胞因子 以器官特异性的方式进行呼吸。 当这是在人类身上完成的时候 白细胞介素-11显著异常。 其中包括： a）细支气管周围结节性炎性浸润，B）上皮下 c）肺泡区域中的肺气肿;以及 d）气道对乙酰甲胆碱的高反应性。 进一步 为了了解这些小鼠气道的形态，我们建议 使用体内显微镜中心来表征 转基因（+）和转基因（-）动物。 希望这一 这种方法将使我们能够区分重塑和发育不全。 其他细胞因子对气道发育和结构的影响 将以类似的方式进行分析。

The asthmatic diathesis is characterized by chronic airway inflammation. In vivo and in vitro studies have demonstrated the disregulation of a wide variety of cytokines in the asthmatic airway. However, in most circumstances, the ability of individual cytokines to mediate the pathologic and physiologic derangements characteristic of this disorder are poorly understood. to address this issue, we have developed a system that allows us to express cytokines in the murine airway in an organ-specific fashion. When this was done with human interleukin-11, prominent abnormalities were noted. They included: a) peribronchiolar nodular inflammatory infiltrates, b) subepithelial fibrosis with airway remodeling; c) emphysema in alveolar areas; and d) airways hyper-responsiveness to methacholine. To further understand the morphology of the airways of these mice, we propose to use the Center for In Vivo Microscopy to characterize the airways of transgene (+) and transgene (-) animals. It is hoped that this approach will enable us to differentiate remodeling from hypoplasia. The effects of other cytokines on airway development and structure will be analyzed in a similar fashion.