Bronchiolitis obliterans with organizing pneumonia (BOOP) is a term for a long observed, but unclassified pattern of acute lung injury. In humans, BOOP is characterized by fibrosis of small airways with fibrous extension into the alveolar spaces with preservation of alveolar ducts and walls. It is frequently associated with a peribronchiolar organizing pneumonia. The lesions may also be accompanied by lipid-laden foamy alveolar macrophages trapped in the air spaces by the fibrosis and by a T cell rich lymphocytic interstitial infiltrate in the regions of the lung directly affected by the lesion. Also, necrosis and sloughing of epithelial cells has been observed and is thought to result in the partial alveolar collapse seen in human BOOP. While BOOP can be associated with documented viral and bacterial infections, many cases are not associated with known causes and are thus classified as idiopathic. Little is known concerning the pathogenesis and treatment of BOOP since no animal models were available for this disorder. The investigators are the first to establish an experimental animal model for this disease. In this model, CBA/J mice infected with reovirus serotype 1/strain Lang develop BOOP lesions which closely resemble the histopathological picture of human BOOP. In addition, the development of BOOP lesions in CBA/J mice is virus strain specific. The central hypothesis of this proposal is that """"""""Disruption of the epithelial basement membrane determines the susceptibility to fibrosis"""""""". The investigators propose to characterize the host and/or viral factors (both immune and non-immune cellular populations) that result in initiation of damage to the basement membrane and relate these finding to the development of fibrosis.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
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Lung Biology and Pathology Study Section (LBPA)
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Lambert, Linda C
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Medical University of South Carolina
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