Abstract
Objectives:
Identifying the inflammatory cells mediating laryngotracheal stenosis (LTS) could allow for identification and modulation of specific immune mechanisms to reduce the development of airway fibrosis. The objective of this study is to (1) introduce a novel mouse model of LTS and 92) define the inflammatory cell infiltrate preceding fibrosis.
Methods:
The experimental design was a 21-day prospective controlled in-vivo in-situ animal study. The mouse laryngotracheal complex was chemomechanically injured with a bleomycin-coated wire brush. Mice were sacrificed at 7, 14, and 21 days. Specimens were examined using histology to assess mucosal inflammation and fibrosis. Immunohistochemistry (IHC) and gene expression analysis were performed to delineate inflammatory cells. Results were compared with 2 control groups: (1) mice with no tracheal injury; and (2) mice that underwent tracheal injury with a saline-coated wire brush.
Results:
Histology demonstrated progressive thickening of the subepithelial lamina propria with an increased inflammatory infiltrate including lymphocytes, neutrophils, and macrophages that peaked at Day 7. This transitioned to resolving inflammation and initial fibrosis by Day 14 with progression of fibrosis to day 21. Gene expression and IHC confirmed increased T-cells and macrophages compared to controls. IHC staining was positive for CD4+ T-lymphocytes.
Conclusions:
Chemomechanical injury of the mouse trachea in situ was successful and may be used as a model to study LTS. Bleomycin accelerates fibrosis as compared to controls with saline-coated wire brush injury. Macrophages and CD4+ T-lymphocytes precede the development of fibrosis in this mouse model and should be further investigated as mediators of LTS.
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