The objective of this research is to investigate the cellular and tissue mechanisms responsible for bronchiolar hypoplasia and alveolar dysplasia that result from viral bronchiolitis and pneumonia during early life. Rats infected with parainfluenza type 1 (Sendai) virus are the animal model used. Morphometric and autoradiographic methods are being used to investigate changes in cell proliferation and cell numbers that occur during postnatal lung growth and that are altered by viral-induced tissue damage and inflammation. In addition, the long-term effects of viral bronchiolitis on pulmonary function and airway hyperreactivity in rats are being assessed. Inbred strains of rats that vary in their susceptibility to viral bronchiolitis will be identified for future studies aimed at investigating genetic and immunological mechanisms that are important in controlling the development of pathologic sequelae to viral bronchiolitis in infancy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL033441-07
Application #
3345361
Study Section
Pathology A Study Section (PTHA)
Project Start
1987-01-01
Project End
1992-12-31
Budget Start
1991-01-18
Budget End
1991-12-31
Support Year
7
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Uhl, E W; Moldawer, L L; Busse, W W et al. (1998) Increased tumor necrosis factor-alpha (TNF-alpha) gene expression in parainfluenza type 1 (Sendai) virus-induced bronchiolar fibrosis. Am J Pathol 152:513-22
Uhl, E W; Castleman, W L; Sorkness, R L et al. (1996) Parainfluenza virus-induced persistence of airway inflammation, fibrosis, and dysfunction associated with TGF-beta 1 expression in brown Norway rats. Am J Respir Crit Care Med 154:1834-42
Sorden, S D; Castleman, W L (1995) Virus-induced increases in airway mast cells in brown Norway rats are associated with enhanced pulmonary viral replication and persisting lymphocytic infiltration. Exp Lung Res 21:197-213
Sorden, S D; Castleman, W L (1995) Virus-induced increases in bronchiolar mast cells in Brown Norway rats are associated with both local mast cell proliferation and increases in blood mast cell precursors. Lab Invest 73:197-204
Cypcar, D; Lemanske Jr, R F (1994) Asthma and exercise. Clin Chest Med 15:351-68
Sorden, S D; Castleman, W L (1991) Brown Norway rats are high responders to bronchiolitis, pneumonia, and bronchiolar mastocytosis induced by parainfluenza virus. Exp Lung Res 17:1025-45
Sorden, S D; Lemanske Jr, R F; Castleman, W L (1990) Pulmonary eosinophilia and granulomatous pulmonary arteritis induced in rats by intravenous Sephadex. Vet Pathol 27:217-22
Castleman, W L; Sorkness, R L; Lemanske Jr, R F et al. (1990) Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness. Am J Pathol 137:821-31
Castleman, W L; Owens, S B; Brundage-Anguish, L J (1989) Acute and persistent alterations in pulmonary inflammatory cells and airway mast cells induced by Sendai virus infection in neonatal rats. Vet Pathol 26:18-25
Castleman, W L; Northrop, P J; McAllister, P K (1989) Replication of parainfluenza (Sendai) virus in isolated rat pulmonary type II alveolar epithelial cells. Am J Pathol 134:1135-42

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