VIRUS-INDUCED CHANGES IN AIRWAY EPITHELIAL FUNCTION

病毒引起的气道上皮功能变化

• 批准号: 2223439
• 负责人: David B Jacoby
• 金额: $ 11.98万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2223439
• 关键词: Macaca mulatta; asthma; biological fluid transport; bronchospasm; cell cell interaction; chloride channels; endopeptidases; enzyme mechanism; ferrets; guinea pigs; ion transport; muscle contraction; organ culture; parainfluenza virus type 1; prostaglandin endoperoxide synthase; prostaglandins; respiratory epithelium; respiratory virus; secretion; smooth muscle; sodium channel; substance P; tachykinin; tissue /cell culture; virus cytopathogenic effect; virus infection mechanism

This project deals with the effect of viral infection on the function of the airway epithelial cell, the primary target of most respiratory viruses. Alterations in both epithelial-smooth interactions and epithelial ion transport will be studied. I have demonstrated that decreased epithelial neutral endopeptidase is responsible for the increased airway smooth muscle response to substance P seen with viral infections. In this project I will examine the effect of viral infections on the response to other peptide mediators, both excitatory and inhibitory and the role of decreased neutral endopeptidase in these responses. Furthermore, I will examine the role of endogenous tachykinins (whose activities are increased in the absence of neutral endopeptidase) in causing the increased parasympathetic bronchoconstriction characteristic if viral airway infection. I will also determine the effect of viral infection on the release of epithelial mediators that increase or decrease smooth muscle contraction. In studying epithelial ion transport, which regulates water secretion, I will first determine the effect of viral infection on baseline (unstimulated) sodium absorption and chloride secretion, and the dependence of such changes on epithelial prostaglandin production. I will also examine the effect of viral infection on paracellular (between cells) and transcellular (through) ion permeability. Finally, I will determine the effect of decreased epithelial neutral endopeptidase on the ion transport response to tachykinins and other peptide mediators. These studies should lead to a greater understanding of the role of viral infections in airway hypersecretion and smooth muscle hyperresponsiveness, as well as insights into the pathophysiologic mechanisms of asthma. This may ultimately provide the basis for new therapeutic strategies.

本项目研究病毒感染对细胞功能的影响