Related Experiment Video
Updated: Jun 3, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Colonic anastomotic healing in the context of altered macrophage function and endotoxemia
Dimitrios Pantelis1, Anke Beissel, Philip Kahl
1Department of Surgery, Rheinische Friedrich-Wilhelms-University Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
Purpose:
Prevention of perioperative activation of intestinal muscularis macrophages is a promising intervention to avoid post-traumatic gastrointestinal tract dysfunction. However, impaired macrophage function could have deleterious consequences on anastomotic healing, especially in complications aggravating the healing process itself, such as infectious problems either as preexisting local inflammation or infection (e.g., complicated diverticulitis) or endotoxemia due to early postoperative infections (e.g., pneumonia). Aim of this study was to investigate colonic anastomotic healing in macrophage-depleted mice in the presence of endotoxemia.
Methods:
Colonic anastomoses were performed, and mice were randomized into six groups (wild type; wild type with endotoxemia; pharmacological depletion of macrophages; pharmacological depletion with endotoxemia; genetically conditioned within the gut muscularis macrophage-deficient osteopetrotic mice; osteopetrotic mice with endotoxemia). Anastomotic tissues were removed 2, 5, and 10 days after surgery and used for functional, histological, biochemical, and molecular investigations.
Results:
After pharmacological pretreatment, an almost complete depletion of macrophages was found in the muscularis up to 24 h postoperatively. Bursting pressure was significantly lower than 10 days after anastomotic procedure in osteopetrotic mice during endotoxemia, in marked contrast to transient pharmacologically macrophage-depleted mice. Pharmacological depletion during endotoxemia did not affect hydroxyproline concentration. Finally, in osteopetrotic mice during endotoxemia, collagen-3 expression was significantly lower compared to controls.
Conclusions:
In our current model, we demonstrate that perioperative pharmacological macrophage depletion and inactivation transiently diminishes muscularis macrophages and does not affect intestinal anastomotic healing in the presence of endotoxemia. However, a long-lasting macrophage absence or dysfunction impairs anastomotic healing and could be a risk factor for postoperative anastomotic leakage.
Insights
Transiently depleting macrophages aids intestinal healing during endotoxemia. However, long-term absence of these immune cells impairs anastomotic healing, increasing leakage risk.
Area of Science:
- Gastroenterology
- Immunology
- Surgical Research
Background:
- Perioperative macrophage activation in the gut can lead to dysfunction.
- Impaired macrophage function may compromise anastomotic healing, particularly with infections or endotoxemia.
Purpose of the Study:
- To investigate colonic anastomotic healing in macrophage-depleted mice under endotoxemia.
- To assess the impact of transient versus long-lasting macrophage absence on healing.
Main Methods:
- Colonic anastomoses were created in mice randomized into six groups, including wild-type and osteopetrotic (macrophage-deficient) models.
- Mice were subjected to endotoxemia, and tissues were analyzed at 2, 5, and 10 days post-surgery.
Main Results:
- Pharmacological depletion transiently reduced muscularis macrophages.
- Osteopetrotic mice with endotoxemia showed significantly lower bursting pressure and collagen-3 expression compared to controls.
- Transient pharmacological depletion did not impair healing in endotoxemic mice.
Conclusions:
- Perioperative pharmacological macrophage depletion is transient and does not impede intestinal anastomotic healing during endotoxemia.
- Prolonged macrophage absence or dysfunction significantly impairs anastomotic healing, posing a risk for leakage.
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
01:18Dysbiosis of the Gut Microbiota
01:12Chronic Inflammation: Introduction