Date of Award

1998

Embargo Period

8-1-2024

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology and Immunology

College

College of Graduate Studies

First Advisor

Steven D. London

Second Advisor

Russell A. Harley

Third Advisor

Lucille London

Fourth Advisor

Maria Trojanowska

Fifth Advisor

William Tyor

Abstract

Inflammatory lung diseases cause a significant amount of morbidity and mortality. However, the mechanisms that control the initiation and resolution of pulmonary inflammatory responses have not been well-elucidated. Histopathological data suggests that the lung responds with a similar pattern of inflammation to diverse range of injurious stimuli. In order to investigate the immunopathogenesis of lung inflammation, a series of in vivo models of lung inflammation were generated in CBA/J and CD-I mice by respiratory reovirus 1/L infection. Using this approach, it was observed in CBA/J mice that a relatively low titer of reovirus 1/L induced a pattern of intraluminal fibrosis in the bronchoalveolar compartment of the lung that is characteristic of the disorder bronchiolitis obliterans organizing pneumonia (BOOP). When higher titers of reovirus 1/L were used to inoculate CBA/J mice, most animals developed acute respiratory distress syndrome (ARDS), which is characterized by widespread vascular endothelial and respiratory epithelial cell damage. Conversely, the pulmonary response of CD-1 mice to respiratory reovirus 1/L was not acute or fibrotic, but instead was characterized by a bronchiocentric, lymphocytic cellular infiltrate that recapitulates the disorder follicular bronchiolitis (FB). FB was also described as a simultaneous component of the inflammatory response in CBA/J mice in addition to BOOP and ARDS. Collectively the models of reovirus 1/L-induced FB, BOOP, and ARDS represent a spectrum of inflammatory lung disorders that are generated by one agent, thus allowing the exploration of cellular and molecular mechanisms that regulate the pulmonary inflammatory response.

Rights

All rights reserved. Copyright is held by the author.

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