AIRWAY SECRETION IN RECURRENT AIRWAY OBSTRUCTION

该项目的目标是量化反复呼吸道阻塞(RAO)的马的呼吸道分泌活动，研究导致呼吸道分泌物增加和积累的机制，并评估这种增加的功能意义。马RAO模拟了人类疾病中观察到的许多变化，如慢性哮喘、慢性支气管炎和有机粉尘引起的呼吸道疾病，在这些疾病中，持续粘液过度生产是呼吸道阻塞的重要组成部分。将利用免疫化学、形态计量学、功能和体外方法来确定与对照相比，受疾病影响的马在粘液/粘液样物质的产生、分泌和上皮内储存方面的时间变化，并评估任何此类变化的功能意义。此外，还将通过评估中性粒细胞弹性蛋白酶和内毒素对呼吸道分泌活性的影响来探讨分泌增加的机制。我的一般假设是，马RAO与粘液产生的持续增加有关，粘液产生即使在明显的疾病缓解期间也会导致呼吸道阻塞，上皮内储存的增加伴随着这种持续增加，以及炎性介质中性粒细胞弹性蛋白酶浓度的增加或对该介质的超敏有助于增加分泌活性。

The goal of this project is to quantify airway secretory activity in horses with recurrent airway obstruction (RAO), to investigate mechanisms underlying increased production and accumulation of airway secretions, and to assess the functional significance of this increase. Equine RAO mimics many of the changes observed in human diseases, such as chronic asthma, chronic bronchitis, and organic dust-induced airway disease, in which persistent mucus overproduction is an important component of airway obstruction. Immunochemical, morphometric, functional, and in vitro methods will be utilized to identify temporal alterations in the production, secretion, and intraepithelial storage of mucus/mucus-like material in disease-affected horses versus controls, and to assess the functional significance of any such alterations. In addition, mechanisms of increased secretion will be addressed by evaluating the effect of neutrophil elastase and endotoxin on airway secretory activity. It is my general hypothesis that equine RAO is associated with a persistent increase in mucus production that contributes to airway obstruction even during periods of apparent disease remission, that increased intraepithelial storage accompanies this persistent increase, and that increased concentrations of the inflammatory mediator neutrophil elastase or a hypersensitivity to this mediator contributes to increased secretory activity.