TY - JOUR
T1 - M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts
AU - Motz, Kevin
AU - Lina, Ioan
AU - Murphy, Michael K.
AU - Drake, Virginia
AU - Davis, Ruth
AU - Tsai, Hsiu Wen
AU - Feeley, Michael
AU - Yin, Linda X.
AU - Ding, Dacheng
AU - Hillel, Alexander
N1 - Funding Information:
Supported by National Institute on Deafness and Other Communication Disorders (NIDCD)/the National Institutes of Health (NIH), award number 1K23DC014082 ( a.h .); and by the Triological Society and American College of Surgeons ( a.h .) as well as a T32 NIH training grant ( k.m .).The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Funding Information:
Research reported in this publication was supported by National Institute on Deafness and Other Communication Disorders of the National Institutes of Health under award number 1K23DC014082 ( a.h .). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This study was also financially supported by the Triological Society and American College of Surgeons ( a.h .) as well as by a T32 NIH training grant ( k.m .).
Publisher Copyright:
© 2020 American Laryngological, Rhinological and Otological Society Inc, The Triological Society and American Laryngological Association (ALA)
PY - 2021/2
Y1 - 2021/2
N2 - Objective: Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte-derived M1 and M2 macrophages on normal airway and LTS-derived fibroblasts (FBs) in vitro. Study Design: Comparative analysis; in vitro controlled study. Methods: Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M-CSF + Interferon-gamma and lipopolysaccharide or Interleukin-4, respectively. FBs isolated from laryngotracheal scar (LTS-FBs) and normal tracheal airway (NA-FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed. Results: Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P =.03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P =.001). In vitro, NA-FBs cultured with M2 macrophages demonstrated a 2.41-fold increase in collagen-1 expression (P =.05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024–2.192, n = 8, P =.015). Conclusion: Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS. Level of Evidence: NA Laryngoscope, 131:E346–E353, 2021.
AB - Objective: Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte-derived M1 and M2 macrophages on normal airway and LTS-derived fibroblasts (FBs) in vitro. Study Design: Comparative analysis; in vitro controlled study. Methods: Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M-CSF + Interferon-gamma and lipopolysaccharide or Interleukin-4, respectively. FBs isolated from laryngotracheal scar (LTS-FBs) and normal tracheal airway (NA-FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed. Results: Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P =.03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P =.001). In vitro, NA-FBs cultured with M2 macrophages demonstrated a 2.41-fold increase in collagen-1 expression (P =.05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024–2.192, n = 8, P =.015). Conclusion: Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS. Level of Evidence: NA Laryngoscope, 131:E346–E353, 2021.
KW - Laryngotracheal stenosis, fibroblasts, M2 macrophages
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U2 - 10.1002/lary.28980
DO - 10.1002/lary.28980
M3 - Article
C2 - 33051870
AN - SCOPUS:85089521554
SN - 0023-852X
VL - 131
SP - E346-E353
JO - Laryngoscope
JF - Laryngoscope
IS - 2
ER -