Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

Abstract

Peritoneal adhesions commonly occur after abdominal or pelvic surgery. These scars join internal organs to each other or to the cavity wall and can present with abdominal or pelvic pain, and bowel obstruction or female infertility. The mechanisms underlying adhesion formation remain unclear and thus effective treatments are not forthcoming. Peritoneal macrophages accumulate after surgery and previous studies have attributed either pro- or anti-scarring properties to these cells. We propose that there are complex and nuanced responses after surgery with respect to both resident and monocyte-derived peritoneal macrophage subpopulations. Moreover, we contend that differences in responses of specific macrophage populations, in part, explain the risk of developing peritoneal scars. We characterised alterations in peritoneal macrophage subpopulations after surgery-induced injury using two strains of mice, BALB/c and C57BL/6, with known differences in macrophage response post-infection. At 14 days post-surgery, BALB/c mice displayed more adhesions compared with C57BL/6 mice. This increase in scarring correlated with a lower influx of monocyte-derived macrophages at day 3 post-surgery. Moreover, BALB/c mice showed distinct macrophage repopulation dynamics after surgery. To confirm a role for monocyte-derived macrophages, we used Ccr2-deficient mice as well as antibody-mediated depletion of CCR2 expressing cells during initial stages of adhesion formation. Both Ccr2-deficient and CCR2-depleted mice showed a significant increase in adhesion formation associated with the loss of a peritoneal monocyte influx. These findings reveal an important protective role for monocyte-derived cells in reducing adhesion formation after surgery.

Fate‐mapping studies in inbred mice: A model for understanding macrophage development and homeostasis?

“…Even if one accepts the interpretation of fate-mapping models and ignores the likely impacts of environment on macrophage turnover, there remains the caveat that the current models are either based on a single inbred mouse strain (C57BL6/J) or the likely effect of genetic background is not considered. Among the few studies that have addressed this question, comparison of serosal macrophage populations in C57BL/6J versus BALB/c mice provided evidence for differential contributions of monocytes and macrophage turnover in the two strains [105,106]. Furthermore, assessment of the relative contribution of embryonic cells to adult macrophage populations depends upon the promoter used to drive cre recombinase and is open to interpretation.…”

Monocyte-derived peritoneal macrophages protect C57BL/6 mice against surgery-induced adhesions

“…We would also like to thank Dr. Gareth Howell from the flow cytometry facility, staffs in the Bioimaging facility and BSF facility at the University of Manchester, and Stella Pearson for technical assistence sectioning histology samples. Some aspects of this manuscript have previously been released as a preprint ( 41 ).…”