Preventive role of CD163-positive macrophages in postoperative peritoneal adhesions

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.

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.

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.

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.