ALTERATIONS IN AIRWAY MUCIN DURING INFLUENZA INFECTION

我的研究兴趣集中在病毒感染对人的影响 呼吸道中的粘液分泌。组织化学研究表明 粘液产生细胞染色特性的改变 (粘膜下腺的杯状细胞和粘液细胞) 感染，表明粘蛋白的生化成分发生了变化。 形态研究已经描述了杯状细胞中粘蛋白的耗竭。 在病毒感染和恢复期间杯状细胞的增殖 感染。这些发现表明，病毒诱导的细胞过度分泌 粘液。在这个项目的第一阶段，我建议将 流感期间和流感后粘蛋白的质和量变化 感染。在第二阶段，我将研究产生 这些变化。 雪貂是流感研究中公认的模型，将被用于 用于这些研究。利用组织化学和形态计量技术， 病毒引起的粘液分泌元件的变化将是 量化的。然后，将感染和感染的小鼠的气管和支气管外植体 单细胞培养的雪貂将与放射性标记的雪貂前体平衡 粘液。分泌的粘蛋白将通过自动柱进行纯化 层析和定量。感染病毒的相对分泌率 对照上皮细胞将在基线下进行评估和刺激 条件。分离的粘液糖蛋白将用 在组成、大小、酸性和分子相互作用方面。 在评估了分泌率和生化指标的变化后 粘液的特性，我将对其机理进行探讨(S) 通过选择性地模仿和阻断潜在的神经和 炎症影响(如肾上腺素能和胆碱能药、代谢物 花生四烯酸、蛋白酶)。一旦确立，这些技术可以 适用于其他呼吸道感染。 继发于高分泌的粘液堆积，可能是 粘蛋白的物理化学性质的改变导致了许多 急性病毒感染的症状，可能是一个主要的潜在原因 与这些疾病相关的发病率和死亡率的原因。 了解鼻咽癌黏液分泌变化的性质和机制 感染病毒的上皮细胞最终将提供机会 开发出更合理、更有效的治疗方法 症状和主要并发症的较好预防。

My research interests center around the effects of viral infections on mucus secretion in the airways. Histochemical studies have shown alterations in the staining characteristics of the mucus-producing cells (goblet cells and mucous cells of the submucosal glands) during chronic infections, suggesting changes in the biochemical composition of mucin. Morphologic studies have described depletion of mucin in goblet cells during viral infection and hyperplasia of goblet cells during recover from infection. These findings suggest a viral-induced hypersecretion of mucin. During Phase I of this project, I propose to characterize the qualitative and quantitative changes in mucin during and after influenza infection. During Phase II, I will investigate the mechanisms producing these changes. The ferret, a well-established model for influenza studies, will be used for these studies. Using histochemical and morphometric techniques, the viral induced changes in the mucus secreting elements will be quantitated. Then, tracheal and bronchial explants of infected and unifected ferrets will be equilibrated with radiolabelled precursors of mucins. Secreted mucins will be purified by automated column chromatography and quantified. The relative rates of secretion of infected and control epithelium will be assessed under baseline and stimulated conditions. Isolated mucous glycoproteins will be characterized with respect to composition, size, acidic properties, and molecular interactions. After assessing alterations of the secretory rate and biochemical characteristics of the mucus, I will investigate mechanism(s) for these changes by selectively mimicking and blocking potential neural and inflammatory influences (eg, adrnergic and cholinergic agents, metabolites of arachadonic acid, proteinases). One established, these techniques can be applied to other infections of the respiratory tract. Accumulation of mucus secondary to hypersecretion and possibly to alterations of the physicochemical properties of mucin causes much of the symptomatology of acute viral infections and may be a major underlying cause for the morbidity and mortality associated with these illnesses. Understanding the nature and mechanisms of changes in mucus secreted by epithelium infected with virus ultimately will afford opportunities to develop more rational and hopefully more effective therapy of these symptoms and better prevention of the major complications.