HUMAN SUBMUCOSAL GLAND AND BRONCHIOLAR SECRETIONS

描述(直接从应用程序中获取) 囊性纤维化(CF)支气管上皮细胞减少 通透性和增加的Na+吸收，这可能有助于 呼吸道分泌物异常和继发感染，这是典型的CF。 粘膜下腺表达高水平的CFTRmRNA和蛋白，以及 细支气管是慢性阻塞性肺疾病最早的呼吸道阻塞部位，但 这些结构对呼吸道分泌物和液体平衡的贡献 正常肺和CF肺尚不清楚。这项研究项目将评估 支气管粘膜下腺和细支气管腺上皮对哮喘的作用 正常人和囊性纤维化患者呼吸道的液体和粘液平衡。人类 取肺组织的支气管粘膜下腺和细支气管上皮 在临床指征的肺切除和肺切除术中来自非CF和CF患者 将对移植手术进行评估。粘膜下腺的结构 细支气管的细胞分布将通过形态计量学进行评估 粘膜下腺浆液细胞、粘液的特异性技术和标记 细胞和纤毛细胞，以及收集导管和 纤毛导管。细支气管上皮细胞将被鉴定为 纤毛状、高脚杯状或克拉拉状，基于特定抗体识别。 离子转运蛋白cftr和cftr的表达及细胞定位 人上皮细胞Na+通道的α、β和伽马亚基将是 用原位杂交和免疫组织化学方法检测。粘膜下层 将测量腺体分泌量、离子组成和调节。 使用体积吸管、离子选择性微电极和人体 粘蛋白特异性酶联免疫吸附试验。细支气管上皮电势差，呼吸道 将评估表面液体离子含量和离子传输规则。 活体电位差静电计，离子选择性 微电极，以及转运激动剂和抑制剂。这些形态测量仪， 基因定位和生理学方法将允许我们测试 粘膜下腺分泌物数量减少的假说 囊性纤维化和定位细支气管区的主要盐分 水的吸收就会发生。这提高了对人类的理解 粘膜下腺和细支气管腺生理学可能阐明 囊性纤维化异常，易接受新的治疗方法 接近了。

DESCRIPTION (Taken directly from the application) Cystic fibrosis (CF) bronchial epithelial cells have decreased Cl permeability and increased Na+ absorption, which may contribute to the abnormal airway secretions and secondary infection that typifies CF. Submucosal glands express high levels of CFTR mRNA and protein, and bronchioles are the site of earliest airway obstruction in CF, but the contributions of these structures to airway secretions and fluid balance in normal and CF lungs are not known. This research project will assess the contributions of bronchial submucosal glands and bronchiolar epithelium to fluid and mucus balance in normal and cystic fibrosis human airways. Human bronchial submucosal glands and bronchiolar epithelium from lungs removed from non-CF and CF patients during clinically indicated lung resection and transplant operations will be evaluated. The structure of submucosal glands and cellular distribution of bronchioles will be assessed by morphometric techniques and markers specific for submucosal gland serous cells, mucous cells, and ciliated cells, and morphologic criteria for collecting ducts and ciliated ducts. Bronchiolar epithelial cells will be identified as ciliated, goblet, or Clara on the basis of specific antibody recognition. The expression and cellular location of the ion transport proteins CFTR and alpha, beta, and gamma subunits of the human epithelial Na+ channel will be determined by in situ hybridization and immunohistochemistry. Submucosal gland secretion volume, ion composition, and regulation will be measured using volume pipettes, ion-selective microelectrodes, and a human mucin-specific ELISA. Bronchiolar epithelial potential difference, airway surface liquid ion content, and ion transport regulation will be assessed with in vivo potential difference electrometers, ion-selective microelectrodes, and transport agonists and inhibitors. These morphometric, gene localization, and physiologic approaches will permit us to test the hypothesis that submucosal gland secretions are decreased in quantity in cystic fibrosis and to localize the bronchiolar region in which major salt and water absorption takes place. This improved understanding of human submucosal gland and bronchiolar physiology may elucidate mechanisms that are abnormal in cystic fibrosis and amenable to novel therapeutic approaches.