© 2003 American Thoracic Society DOI: 10.1165/rcmb.4891 Differential Role for T Cells in the Development of Fibrotic Lesions Associated with Reovirus 1/L-Induced Bronchiolitis Obliterans Organizing Pneumonia versus Acute Respiratory Distress SyndromeDepartments of Microbiology and Immunology and of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina Address correspondence to: Dr. Lucille London, Ph.D., Department of Microbiology and Immunology, Medical University of South Carolina, 173 Ashley Avenue, P.O. Box 250504, Charleston, South Carolina 29425. E-mail: londonl{at}musc.edu
Bronchiolitis obliterans organizing pneumonia (BOOP) and Acute Respiratory Distress Syndrome (ARDS) are two pulmonary diseases with fibrotic components. BOOP is characterized by perivascular/peribronchiolar leukocyte infiltration leading to the development of intra-alveolar fibrosis. ARDS is a biphasic disease that includes an acute phase, consisting of severe leukocyte infiltration, edema, hemorrhage, and the formation of hyaline membranes, and a chronic phase, which is characterized by persistent intra-alveolar and interstitial fibrosis. CBA/J mice infected with 1 x 106 plaque-forming units (pfu) reovirus 1/L develop follicular bronchiolitis and intra-alveolar fibrosis similar to BOOP. In contrast, CBA/J mice infected with 1 x 107 pfu reovirus 1/L develop histologic characteristics of ARDS including diffuse alveolar damage, hyaline membranes, and intra-alveolar fibrosis. In this report, we demonstrate a differential role for T lymphocytes in the development of fibrosis associated with BOOP versus ARDS. Neonatally thymectomized CBA/J mice infected with 1 x 107 pfu (ARDS) reovirus 1/L still develop the hallmark characteristics of ARDS, including a severe viral pneumonia with cellular infiltrates comprised mainly of macrophages and neutrophils, hyaline membrane formation, and hemorrhage during the acute phase of the disease and persistent intra-alveolar fibrosis during the chronic phase of the disease. In contrast, neonatally thymectomized CBA/J mice infected with 1 x 106 pfu (BOOP) reovirus 1/L do not develop intra-alveolar fibrosis associated with BOOP. Therefore, while T cells are necessary for the development of intraluminal fibrosis associated with BOOP, they are not necessary for the development of intraluminal fibrosis associated with ARDS. Furthermore, we suggest that interferon-
Abbreviations: acute respiratory distress syndrome, ARDS • bronchoalveolar lavage, BAL • bronchoalveolar lavage fluid, BALF • bronchiolitis obliterans organizing pneumonia, BOOP • follicular bronchiolitis, FB • interferon, IFN • IFN-inducible protein, IP • intranasal, i.n. • idiopathic pulmonary fibrosis, IPF • monoclonal antibodies, mAb • monocyte chemoattractant protein, MCP • migration inhibitory factor, MIF • messenger RNA, mRNA • neonatally thymectomized, nTx • plaque-forming units, pfu • regulated on activation normal T cell expressed and secreted, RANTES • RNase protection assay, RPA • transforming growth factor, TGF This article has been cited by other articles:
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plays a key role in the fibrotic process and that elevated levels of interferon-
