AIRWAY MORPHOLOGY IN IL 11 OVEREXPRESSION TRANSGENIC MICE

哮喘素质以慢性呼吸道为特征 发炎。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，单个细胞因子能够 调节以病理和生理紊乱为特征的 人们对这种疾病知之甚少。为了解决这个问题，我们有 开发了一种系统，允许我们在小鼠体内表达细胞因子 以器官特有的方式呼吸道。当这是在人类身上做的 白介素11，显著异常。这些建议包括： A)细支气管周围结节炎性浸润物，b)上皮下 纤维化伴呼吸道重塑；c)肺泡区的肺气肿； D)呼吸道对乙酰甲胆碱高反应性。为了进一步 为了了解这些小鼠的呼吸道形态，我们建议 使用活体显微镜中心来确定呼吸道的特征 转基因(+)和转基因(-)动物。希望这是一次 方法将使我们能够区分重塑和发育不全。 其他细胞因子对呼吸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.