TY - JOUR
T1 - Alterations in macrophage polarization in injured murine vocal folds
AU - Kaba, Shinji
AU - Nakamura, Ryosuke
AU - Yamashita, Masaru
AU - Katsuno, Tatsuya
AU - Suzuki, Ryo
AU - Tateya, Ichiro
AU - Kishimoto, Yo
AU - Omori, Koichi
N1 - Funding Information:
This study was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and GSK Japan Research Grant 2016. The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Publisher Copyright:
© 2018 The American Laryngological, Rhinological and Otological Society, Inc.
PY - 2019/4
Y1 - 2019/4
N2 - Objectives: Macrophages are prominent inflammatory cells in wounds, and their phenotypes are altered during wound healing. They are reported to contribute to not only inflammatory responses but also tissue remodeling. However, few studies in vocal fold biology have focused on the function of macrophages. The purpose of this study was to investigate macrophage polarization and distribution in injured murine vocal folds. Study Design: Animal experiments with controls. Method: Unilateral vocal fold stripping was performed on C57BL/6 mice, and larynges were harvested 1, 3, 5, 7, and 14 days postinjury. Immunohistochemical analysis of the vocal fold lamina propria was performed to detect the expression of classically activated (M1) and alternatively activated (M2) macrophage markers (inducible nitric oxide synthase [iNOS] and CD206, respectively) in F4/80 + macrophages. Results: The proportion of F4/80 + iNOS + cells out of all F4/80 + cells tended to increase from day 1. F4/80 + iNOS + cell percentage tended to be high at days 1 through 7 and declined to close to a normal level by day 14. F4/80 + CD206 + cell percentage tended to decrease at day 1 and then to increase the rest of the time. In the normal vocal fold, the majority of F4/80 + macrophages were only positive for CD206. F4/80 + iNOS + CD206 + cells were observed at days 1 through 7. Conclusion: The main population of injured sites gradually shifted from M1 to M2 marker-positive macrophages in murine vocal folds. However, coexistence of M1 and M2 markers in the same macrophages was observed. Our results suggest that macrophage phenotypes are regulated by complex tissue-derived signals and exhibit dynamic changes during wound healing. Level of Evidence: NA Laryngoscope, 129:E135–E142, 2019.
AB - Objectives: Macrophages are prominent inflammatory cells in wounds, and their phenotypes are altered during wound healing. They are reported to contribute to not only inflammatory responses but also tissue remodeling. However, few studies in vocal fold biology have focused on the function of macrophages. The purpose of this study was to investigate macrophage polarization and distribution in injured murine vocal folds. Study Design: Animal experiments with controls. Method: Unilateral vocal fold stripping was performed on C57BL/6 mice, and larynges were harvested 1, 3, 5, 7, and 14 days postinjury. Immunohistochemical analysis of the vocal fold lamina propria was performed to detect the expression of classically activated (M1) and alternatively activated (M2) macrophage markers (inducible nitric oxide synthase [iNOS] and CD206, respectively) in F4/80 + macrophages. Results: The proportion of F4/80 + iNOS + cells out of all F4/80 + cells tended to increase from day 1. F4/80 + iNOS + cell percentage tended to be high at days 1 through 7 and declined to close to a normal level by day 14. F4/80 + CD206 + cell percentage tended to decrease at day 1 and then to increase the rest of the time. In the normal vocal fold, the majority of F4/80 + macrophages were only positive for CD206. F4/80 + iNOS + CD206 + cells were observed at days 1 through 7. Conclusion: The main population of injured sites gradually shifted from M1 to M2 marker-positive macrophages in murine vocal folds. However, coexistence of M1 and M2 markers in the same macrophages was observed. Our results suggest that macrophage phenotypes are regulated by complex tissue-derived signals and exhibit dynamic changes during wound healing. Level of Evidence: NA Laryngoscope, 129:E135–E142, 2019.
UR - http://www.scopus.com/inward/record.url?scp=85059318368&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85059318368&partnerID=8YFLogxK
U2 - 10.1002/lary.27523
DO - 10.1002/lary.27523
M3 - Article
C2 - 30597576
AN - SCOPUS:85059318368
VL - 129
SP - E135-E142
JO - Laryngoscope
JF - Laryngoscope
SN - 0023-852X
IS - 4
ER -