Celia Flory
Pronouns: she/her
Research Mentor(s): John Osterholzer
Co-Presenter:
Research Mentor School/College/Department: Internal Medicine, Pulmonary Division / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors:
Presenter: 11
Abstract
Title: Sulfur Dioxide Exposure Induces Peribronchiolar Fibrosis in Mice – an Effort to Model Deployment-Related Constrictive Bronchiolitis Authors: C. Flory, K. N. Selbmann, S. Lahiri, S. Teitz-Tennenbaum, K. Siddiqui, A. Ganguly, and J. J. Osterholzer RATIONALE: Deployment-related constrictive bronchiolitis (DRCB), a debilitating medical condition characterized by cough and dyspnea, has been identified in military personnel returning from Southwest Asia. Many of these patients (>70% in one study) reported exposure to smoke from the Al-Mishraq sulfur enrichment facility fire near Mosul, Iraq in 2003. This fire burned for more than a month, releasing over 600 kilotons of sulfur dioxide (SO2), and causing levels to reach as high as 125 ppm. Exposure to burn pit smoke, known to contain SO2, was also described by most patients. The defining histopathological feature of DRCB is fibrosis of small airways in the lung, but additional abnormalities such as chronic peribronchiolar inflammation and respiratory bronchiolitis are observed in many subjects; whether these findings are related to SO2 exposure remains uncertain. The aim of this study was to determine whether SO2 exposure can induce histopathological features of DRCB. METHODS: C57BL/6J mice were exposed to 50 ± 5 ppm SO2 for one hour a day for five consecutive days (day 0-4). Unexposed mice served as controls. Lungs were harvested on day 5, 10, and 20. Leukocyte subpopulations were quantified by flow cytometry analysis. Peribronchiolar immune Infiltrates were evaluated using hematoxylin and eosin-stained lung sections. Collagen content in the walls of small airways (45-400 µm in diameter) was determined by morphometric analysis of Masson’s trichrome-stained sections and by measuring fluorescence intensity of picrosirius red-stained sections, and normalized to the length of the bronchiole basement membrane. Number and density of collagen fibers were calculated using CurveAlign software. Thickness and length of collagen fibers were determined using CT-Fire software. Lung sections of SO2-exposed mice were further compared with those of a Veteran exposed to the Al-Mishraq fire and diagnosed with DRCB. RESULTS: SO2 exposure induced no accumulation of leukocytes in the lung and no peribronchiolar immune infiltrates. However, the area of collagen deposition surrounding the basement membrane of small airways was increased at day 10 and 20 versus day 0 and 5 (by up to 25%, p < 0.05). Moreover, the fluorescence intensity of picrosirius red within walls of small airways was substantially higher at day 20 versus day 0, 5, and 10 (by up to 2.7-fold, p < 0.001). The thickness, length, and number of collagen fibers were increased at day 20, accounting for the observed increase in collagen content. In comparison with DRCB, SO2-exposed mice recapitulated peribronchiolar fibrosis but lacked squamous metaplasia of small airways epithelium, peribronchiolar inflammation, clusters of big, foamy airway macrophages, and pigment deposition. CONCLUSIONS: This protocol of SO2 exposure is sufficient to induce peribronchiolar fibrosis in mice yet failed to elicit other histopathological features of DRBC. While additional SO2 exposure protocols should be assessed, our findings indicate that DRCB may not be solely attributable to SO2 exposure. Presentation link
Biomedical Sciences, Interdisciplinary, Natural/Life Sciences
