VIRUS-INDUCED CHANGES IN AIRWAY EPITHELIAL FUNCTION

这个项目是关于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点 病毒。上皮-平滑相互作用的改变和 我们将研究上皮细胞的离子转运。 我已经证明了上皮中性内肽酶降低是 引起呼吸道平滑肌对物质反应增强的原因 P可见病毒感染。在这个项目中，我将研究其效果 病毒感染对其他多肽介质的反应，两者 兴奋性和抑制性与中性降低的作用 这些反应中的内肽酶。此外，我将研究一下 内源性速激肽(其活性在缺乏时增加 中性内肽酶)在引起副交感神经增加中的作用 呼吸道病毒感染时的支气管收缩特征。这就做 也确定病毒感染对释放的影响 增加或减少平滑肌的上皮性介质 收缩。 在研究调节水分分泌的上皮离子运输时，我 将首先确定病毒感染对基线的影响 (无刺激)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 还将检查病毒感染对细胞旁(之间)的影响 细胞)和跨细胞(通过)离子渗透性。最后，我会 测定上皮中性内肽酶降低对血管内皮生长因子的影响 对速激肽和其他多肽介质的离子转运反应。 这些研究应该会使我们更好地理解 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洞察 哮喘的发病机制。这最终可能为新的 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.