Dysregulated Macrophages Are Present in Bleomycin-Induced Murine Laryngotracheal Stenosis

Alexander T. Hillel, Idris Samad, Garret Ma, Dacheng Ding, Kaitlyn Sadtler, Jonathan D. Powell, Andrew P. Lane, Maureen R. Horton

Research output: Contribution to journalArticle

Abstract

Objective. To define the inflammatory cell infiltrate preceding fibrosis in a laryngotracheal stenosis (LTS) murine model. Study Design. Prospective controlled murine study. Setting. Laboratory. Subjects and Methods. Chemomechanical injury mice (n = 44) sustained bleomycin-coated wire-brush injury to the laryngotracheal complex while mechanical injury controls (n = 42) underwent phosphate-buffered saline (PBS)coated wirebrush injury. Mock surgery controls (n = 34) underwent anterior transcervical tracheal exposure only. Inflammatory and fibrosis protein and gene expression were assessed in each condition. Immunohistochemistry served as a secondary outcome. Results. In chemomechanical injury mice, there was an upregulation of collagen I (P<.0001, P<.0001), Tgf-b (P = .0023, P = .0008), and elastin (P<.0001, P<.0001) on day 7; acute inflammatory gene Il1b (P = .0027, P = .0008) on day 1; and macrophage gene CD11b (P = .0026, P = .0033) on day 1 vs mechanical and mock controls, respectively. M1 marker inducible nitric oxide synthase (iNOS) expression decreased (P = .0014) while M2 marker Arg1 (P = .0002) increased on day 7 compared with mechanical controls. Flow cytometry demonstrated increased macrophages (P = .0058, day 4) and M1 macrophages (P = .0148, day 4; P = .0343, day 7; P = .0229, day 10) compared to mock controls. There were similarities between chemomechanical and mechanical injury mice with an increase in M2 macrophages at day 10 (P = .0196). Conclusions. The bleomycin-induced LTS mouse model demonstrated increased macrophages involved with the development of fibrosis. Macrophage immunophenotype suggested that dysregulated M2 macrophages have a role in abnormal laryngotracheal wound healing. These data delineate inflammatory cells and signaling pathways in LTS that may potentially be modulated to lessen fibroblast proliferation and collagen deposition.

Original languageEnglish (US)
Pages (from-to)244-250
Number of pages7
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume153
Issue number2
DOIs
StatePublished - Aug 25 2015

Keywords

  • airway epithelial injury
  • laryngotracheal stenosis
  • mouse model
  • subglottic stenosis
  • trachea

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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