The international surgical journal with global reach

This is the Scientific Surgery Archive, which contains all randomized clinical trials in surgery that have been identified by searching the top 50 English language medical journal issues since January 1998. Compiled by Jonothan J. Earnshaw, former Editor-in-Chief, BJS

Effects of macrophage‐dependent peroxisome proliferator‐activated receptor γ signalling on adhesion formation after abdominal surgery in an experimental model. BJS 2015; 102: 1506-1516.

Published: 27th August 2015

Authors: G.‐S. Hong, T. Schwandt, K. Stein, B. Schneiker, M. P. Kummer, M. T. Heneka et al.

Background

The pathophysiology of adhesion formation after abdominal and pelvic surgery is still largely unknown. The aim of the study was to investigate the role of macrophage polarization and the effect of peroxisome proliferator‐activated receptor (PPAR) γ stimulation on adhesion formation in an animal model.

Method

Peritoneal adhesion formation was induced by the creation of ischaemic buttons within the peritoneal wall and the formation of a colonic anastomosis in wild‐type, interleukin (IL) 10‐deficient (IL‐10−/−), IL‐4‐deficient (IL‐4−/−) and CD11b‐Cre/PPARγfl/fl mice. Adhesions were assessed at regular intervals, and cell preparations were isolated from ischaemic buttons and normal peritoneum. These samples were analysed for macrophage differentiation and its markers, and expression of cytokines by quantitative PCR, fluorescence microscopy, arginase activity and pathological examination. Some animals underwent pioglitazone (PPAR‐γ agonist) or vehicle treatment to inhibit adhesion formation. Anastomotic healing was evaluated by bursting pressure measurement and collagen gene expression.

Results

Macrophage M2 marker expression and arginase activity were raised in buttons without adhesions compared with buttons with adhesions. IL‐4−/− and IL‐10−/− mice were not affected, whereas CD11b‐Cre/PPARγfl/fl mice showed decreased arginase activity and increased adhesion formation. Perioperative pioglitazone treatment increased arginase activity and decreased adhesion formation in wild‐type but not CD11b‐Cre/PPARγfl/fl mice. Pioglitazone had no effect on anastomotic healing.

Conclusion

Endogenous macrophage‐specific PPAR‐γ signalling affected arginase activity and macrophage polarization, and counter‐regulated peritoneal adhesion manifestation. Pharmacological PPAR‐γ agonism induced a shift towards macrophage M2 polarization and ameliorated adhesion formation in a macrophage‐dependent manner.
Surgical relevance

Postoperative adhesion formation is frequently seen after abdominal surgery and occurs in response to peritoneal trauma. The pathogenesis is still unknown but includes an imbalance in fibrinolysis, collagen production and inflammatory mechanisms. Little is known about the role of macrophages during adhesion formation.

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