Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions

Abstract Background Although abdominal surgeries can be lifesaving, they are often accompanied by the complication of peritoneal adhesion formation. While macrophages contribute to this process, the specific subtypes and underlying mechanisms remain unclear. Methods We aimed to identify and investig...

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Main Authors: Lianbo Li, Hiroki Hirao, Masaki Honda, Ahmad Adawy, Cheng Pan, Yukio Fujiwara, Daiki Yoshii, Weijie Xue, Masahiro Tomita, Jie Su, Taizo Hibi, Yoshihiro Komohara
Format: Article
Language:English
Published: BMC 2025-08-01
Series:Inflammation and Regeneration
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Online Access:https://doi.org/10.1186/s41232-025-00392-3
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author Lianbo Li
Hiroki Hirao
Masaki Honda
Ahmad Adawy
Cheng Pan
Yukio Fujiwara
Daiki Yoshii
Weijie Xue
Masahiro Tomita
Jie Su
Taizo Hibi
Yoshihiro Komohara
author_facet Lianbo Li
Hiroki Hirao
Masaki Honda
Ahmad Adawy
Cheng Pan
Yukio Fujiwara
Daiki Yoshii
Weijie Xue
Masahiro Tomita
Jie Su
Taizo Hibi
Yoshihiro Komohara
author_sort Lianbo Li
collection DOAJ
description Abstract Background Although abdominal surgeries can be lifesaving, they are often accompanied by the complication of peritoneal adhesion formation. While macrophages contribute to this process, the specific subtypes and underlying mechanisms remain unclear. Methods We aimed to identify and investigate the roles of the functional subtypes of macrophages involved in adhesion formation to identify new strategies to combat postoperative peritoneal adhesions. The functional cell types and relevant molecular mechanisms involved in adhesion formation were identified using single-cell RNA sequencing. A human postoperative peritoneal adhesion model derived from appendicitis cases was used to validate the findings. Functional experiments were then conducted using a cecal ligation and puncture mouse model, as well as primary macrophage and mesothelial cell lines. Results The findings led to the identification of a macrophage subpopulation characterized by its role in anti-adhesion formation in postoperative peritoneal adhesions. These findings indicate that CD163-positive macrophages accumulate in not only the serous layer of the primary site of postoperative inflammation, but also the tissues adjacent to the adhesion. In addition, CD163 deficiency appears to promote the formation of postoperative adhesions and acute inflammatory responses, and peritoneal CD163-positive macrophages appear to migrate to the postoperative inflammation site, thereby reducing adhesion formation by decreasing PAI-1 secretion from mesothelial cells, enhancing the fibrinolytic system, and ultimately reducing postoperative adhesions. Conclusions The present findings clarify the interaction between CD163-positive macrophages and mesothelial cells, which play a crucial role in the formation of postoperative peritoneal adhesions.
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spelling doaj-art-97258f7438ca42d9b3a1736b06ef2bf72025-08-20T03:04:26ZengBMCInflammation and Regeneration1880-81902025-08-0145111610.1186/s41232-025-00392-3Preventive role of CD163-positive macrophages in postoperative peritoneal adhesionsLianbo Li0Hiroki Hirao1Masaki Honda2Ahmad Adawy3Cheng Pan4Yukio Fujiwara5Daiki Yoshii6Weijie Xue7Masahiro Tomita8Jie Su9Taizo Hibi10Yoshihiro Komohara11Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Pediatric Surgery and Transplantation, Graduate School of Medical Sciences, Kumamoto UniversityDepartment of Cell Pathology, Graduate School of Medical Sciences, Kumamoto UniversityAbstract Background Although abdominal surgeries can be lifesaving, they are often accompanied by the complication of peritoneal adhesion formation. While macrophages contribute to this process, the specific subtypes and underlying mechanisms remain unclear. Methods We aimed to identify and investigate the roles of the functional subtypes of macrophages involved in adhesion formation to identify new strategies to combat postoperative peritoneal adhesions. The functional cell types and relevant molecular mechanisms involved in adhesion formation were identified using single-cell RNA sequencing. A human postoperative peritoneal adhesion model derived from appendicitis cases was used to validate the findings. Functional experiments were then conducted using a cecal ligation and puncture mouse model, as well as primary macrophage and mesothelial cell lines. Results The findings led to the identification of a macrophage subpopulation characterized by its role in anti-adhesion formation in postoperative peritoneal adhesions. These findings indicate that CD163-positive macrophages accumulate in not only the serous layer of the primary site of postoperative inflammation, but also the tissues adjacent to the adhesion. In addition, CD163 deficiency appears to promote the formation of postoperative adhesions and acute inflammatory responses, and peritoneal CD163-positive macrophages appear to migrate to the postoperative inflammation site, thereby reducing adhesion formation by decreasing PAI-1 secretion from mesothelial cells, enhancing the fibrinolytic system, and ultimately reducing postoperative adhesions. Conclusions The present findings clarify the interaction between CD163-positive macrophages and mesothelial cells, which play a crucial role in the formation of postoperative peritoneal adhesions.https://doi.org/10.1186/s41232-025-00392-3Peritoneal adhesionMacrophageCD163Appendectomy
spellingShingle Lianbo Li
Hiroki Hirao
Masaki Honda
Ahmad Adawy
Cheng Pan
Yukio Fujiwara
Daiki Yoshii
Weijie Xue
Masahiro Tomita
Jie Su
Taizo Hibi
Yoshihiro Komohara
Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions
Inflammation and Regeneration
Peritoneal adhesion
Macrophage
CD163
Appendectomy
title Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions
title_full Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions
title_fullStr Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions
title_full_unstemmed Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions
title_short Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions
title_sort preventive role of cd163 positive macrophages in postoperative peritoneal adhesions
topic Peritoneal adhesion
Macrophage
CD163
Appendectomy
url https://doi.org/10.1186/s41232-025-00392-3
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