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.
| Jefcoat, A M; Hotchkiss, J A; Gerber, V et al. (2001) Persistent mucin glycoprotein alterations in equine recurrent airway obstruction. Am J Physiol Lung Cell Mol Physiol 281:L704-12 |
