title: Colonic anastomotic healing in the context of altered macrophage function and endotoxemia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Rheinische Friedrich-Wilhelms-University Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pantelis
authors.forename: Anke
authors.initials: A
authors.lastname: Beissel
authors.forename: Philip
authors.initials: P
authors.lastname: Kahl
authors.forename: Tim O
authors.initials: TO
authors.lastname: Vilz
authors.forename: Burkhard
authors.initials: B
authors.lastname: Stoffels
authors.forename: Sven
authors.initials: S
authors.lastname: Wehner
authors.forename: Joerg C
authors.initials: JC
authors.lastname: Kalff
mesh_terms: D000714:Anastomosis, Surgical; D000818:Animals; D002452:Cell Count; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003106:Colon / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery*; D019446:Endotoxemia / Q000503:physiopathology*; D006909:Hydroxyproline / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008264:Macrophages / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011182:Postoperative Care; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D006909:Hydroxyproline