HUMAN SUBMUCOSAL GLAND AND BRONCHIOLAR SECRETIONS

人类粘膜下腺和细支气管分泌物

• 批准号: 6056422
• 负责人: JAMES R YANKASKAS
• 金额: $ 21.91万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6056422
• 关键词: animal tissue; bronchial mucus; bronchioles; cell type; chloride channels; cystic fibrosis; enzyme linked immunosorbent assay; histology; histopathology; human tissue; immunocytochemistry; in situ hybridization; mucins; protein structure function; respiratory epithelium; secretion

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.

描述（直接取自应用程序） 囊性纤维化 (CF) 支气管上皮细胞 Cl 降低 渗透性和增加 Na+ 吸收，这可能有助于 气道分泌物异常和 CF 典型的继发感染。 粘膜下腺体表达高水平的 CFTR mRNA 和蛋白质，并且 细支气管是 CF 最早发生气道阻塞的部位，但 这些结构对气道分泌物和液体平衡的贡献 正常肺和 CF 肺尚不清楚。 该研究项目将评估 支气管粘膜下腺和细支气管上皮的贡献 正常和囊性纤维化人类气道中的液体和粘液平衡。 人类 去除肺部的支气管粘膜下腺和细支气管上皮 来自非 CF 和 CF 患者在临床指示的肺切除术中以及 将评估移植手术。 粘膜下腺的结构 细支气管的细胞分布将通过形态测量进行评估 粘膜下腺浆液细胞、粘膜特异性技术和标记 细胞和纤毛细胞，以及集合管和形态学标准 纤毛导管。 细支气管上皮细胞将被鉴定为 基于特异性抗体识别的纤毛状、杯状或克拉拉状。 离子转运蛋白CFTR和的表达和细胞定位 人类上皮 Na+ 通道的 α、β 和 γ 亚基将 通过原位杂交和免疫组织化学测定。 粘膜下层 将测量腺体分泌量、离子成分和调节 使用容量移液器、离子选择性微电极和人体 粘蛋白特异性 ELISA。 细支气管上皮电位差，气道 将评估表面液体离子含量和离子传输调节 带体内电位差静电计，离子选择性 微电极、转运激动剂和抑制剂。 这些形态测量， 基因定位和生理学方法将使我们能够测试 粘膜下腺分泌物数量减少的假设 囊性纤维化并定位主要盐分存在的细支气管区域 并发生吸水。 这增进了对人类的理解 粘膜下腺和细支气管的生理学可能阐明以下机制： 囊性纤维化异常，适合新的治疗 接近。