{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:38:58Z","timestamp":1790948338903,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T00:00:00Z","timestamp":1434499200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aao-hnsfjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Otolaryngol.--head neck surg."],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To define the inflammatory cell infiltrate preceding fibrosis in a laryngotracheal stenosis (LTS) murine model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Prospective controlled murine study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Laboratory.<\/jats:p><\/jats:sec><jats:sec><jats:title>Subjects and Methods<\/jats:title><jats:p>Chemomechanical injury mice (n = 44) sustained bleomycin\u2010coated wire\u2010brush injury to the laryngotracheal complex while mechanical injury controls (n = 42) underwent phosphate\u2010buffered saline (PBS)\u2013coated wire\u2010brush 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In chemomechanical injury mice, there was an upregulation of collagen I (<jats:italic>P<\/jats:italic> &lt;. 0001, <jats:italic>P<\/jats:italic> &lt;. 0001), <jats:italic>Tgf\u2010\u03b2<\/jats:italic> (<jats:italic>P<\/jats:italic> =. 0023, <jats:italic>P<\/jats:italic> =. 0008), and <jats:italic>elastin<\/jats:italic> (<jats:italic>P<\/jats:italic> &lt;. 0001, <jats:italic>P<\/jats:italic> &lt;. 0001) on day 7; acute inflammatory gene <jats:italic>Il1\u03b2<\/jats:italic> (<jats:italic>P<\/jats:italic> =. 0027, <jats:italic>P<\/jats:italic> =. 0008) on day 1; and macrophage gene <jats:italic>CD11b<\/jats:italic> (<jats:italic>P<\/jats:italic> =. 0026, <jats:italic>P<\/jats:italic> =. 0033) on day 1 vs mechanical and mock controls, respectively. M1\u00a0marker inducible nitric oxide synthase (iNOS) expression decreased (<jats:italic>P<\/jats:italic> =. 0014) while M2\u00a0marker <jats:italic>Arg1<\/jats:italic> (<jats:italic>P<\/jats:italic> =. 0002) increased on day 7 compared with mechanical controls. Flow cytometry demonstrated increased macrophages (<jats:italic>P<\/jats:italic> =. 0058, day 4) and M1\u00a0macrophages (<jats:italic>P<\/jats:italic> =. 0148, day 4; <jats:italic>P<\/jats:italic> =. 0343, day 7; <jats:italic>P<\/jats:italic> =. 0229, day 10) compared to mock controls. There were similarities between chemomechanical and mechanical injury mice with an increase in M2\u00a0macrophages at day 10 (<jats:italic>P<\/jats:italic> =. 0196).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The bleomycin\u2010induced LTS mouse model demonstrated increased macrophages involved with the development of fibrosis. Macrophage immunophenotype suggested that dysregulated M2\u00a0macrophages 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.<\/jats:p><\/jats:sec>","DOI":"10.1177\/0194599815589106","type":"journal-article","created":{"date-parts":[[2015,6,17]],"date-time":"2015-06-17T23:31:10Z","timestamp":1434583870000},"page":"244-250","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":53,"title":["Dysregulated Macrophages Are Present in Bleomycin\u2010Induced Murine Laryngotracheal Stenosis"],"prefix":"10.1002","volume":"153","author":[{"given":"Alexander T.","family":"Hillel","sequence":"first","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Idris","family":"Samad","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garret","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dacheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2013Head and Neck Surgery Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Sadtler","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Johns Hopkins University School of Medicine Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan 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