VIRUS-INDUCED CHANGES IN AIRWAY EPITHELIAL FUNCTION

本项目研究病毒感染对细胞功能的影响， 呼吸道上皮细胞是大多数呼吸道疾病的主要靶细胞， 病毒 上皮-平滑相互作用和 将研究上皮离子转运。 我已经证明了上皮中性内肽酶的减少是 负责增加气道平滑肌对物质的反应 P见于病毒感染。 在这个项目中，我将研究 病毒感染对其他肽介质的反应， 兴奋性和抑制性以及中性粒细胞减少的作用 内肽酶在这些反应中。 此外，我还将研究 内源性速激肽（其活性在缺乏 中性内肽酶）引起副交感神经 病毒性呼吸道感染时的支气管收缩特征。 我会 还确定病毒感染对释放的影响， 增加或减少平滑肌的上皮介质 收缩。 在研究调节水分分泌的上皮细胞离子转运时， 将首先确定病毒感染对基线的影响 （未受刺激的）钠吸收和氯化物分泌，以及 这种变化依赖于上皮前列腺素的产生。 我 还将研究病毒感染对细胞旁（ 细胞）和跨细胞（通过）离子渗透性。 最后要 确定减少的上皮中性内肽酶对 对速激肽和其他肽介质的离子转运反应。 这些研究应有助于更好地了解 呼吸道高分泌和平滑肌中的病毒感染 高反应性，以及对病理生理学的见解 哮喘的机制 这可能最终为新的 治疗策略

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.