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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32RR005070-02
Application #
6348539
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1999-09-10
Project End
Budget Start
2000-09-10
Budget End
2001-09-09
Support Year
2
Fiscal Year
2000
Total Cost
$46,300
Indirect Cost
Name
Michigan State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
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