ALTERATIONS IN AIRWAY MUCIN DURING INFLUENZA INFECTION

我的研究兴趣集中在病毒感染对 呼吸道中的粘液分泌。 组织化学研究表明 粘液生成细胞染色特征的改变 （杯状细胞和粘膜下腺体的粘液细胞） 感染，表明粘蛋白的生化组成的变化。 形态学研究已经描述了杯状细胞中粘蛋白的耗竭 在病毒感染和杯状细胞增生期间， 感染 这些发现表明病毒诱导的 粘蛋白。 在该项目的第一阶段，我建议将 流感期间和之后粘蛋白的定性和定量变化 感染 在第二阶段，我将研究产生 这些变化。 雪貂是一种已建立的流感研究模型， 对于这些研究。 采用组织化学和形态计量学技术， 病毒引起的粘液分泌元件的变化将是 定量。 然后，气管和支气管外植体的感染和 未受感染的雪貂将与放射性标记的前体平衡， 粘蛋白。 分泌的粘蛋白将通过自动柱纯化 层析并定量。 感染者的相对分泌率 和对照上皮将在基线下进行评估， 条件 分离的粘液糖蛋白的特征在于 在组成、尺寸、酸性和分子相互作用方面。 在评估分泌率和生化指标的变化后， 粘液的特性，我将研究这些机制（S） 通过选择性地模仿和阻断潜在的神经和 炎症影响（例如，肾上腺素能和胆碱能药物、代谢物 花生四烯酸、蛋白酶）。 一个既定的，这些技术可以 适用于其他呼吸道感染。 粘液积聚继发于分泌过多，并可能 粘蛋白的物理化学性质的改变引起了许多 急性病毒感染的病原学，可能是一个主要的潜在的 与这些疾病相关的发病率和死亡率的原因。 了解分泌粘液的性质和机制的变化， 感染病毒的上皮细胞最终将提供机会， 开发更合理、更有效的治疗方法 症状和更好地预防主要并发症。

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.