title: Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.
abstract: BACKGROUND
  Peritoneal injury sustained at laparotomy may evoke local inflammatory responses that result in adhesion formation. Peritoneal mast cells are likely to initiate this process, whereas vascular permeability/endothelial growth factor (VEGF) may facilitate the degree to which subsequent adhesion formation occurs.
  
  
  METHODS
  Mast cell deficient mice (WBB6F1-/-), along with their mast cell sufficient counterparts (WBB6F1+/+), underwent a standardized adhesion-inducing operation (AIS) with subsequent sacrifice and adhesion assessment 14 days later in a blinded fashion. Additional CD-1 and WBB6F1+/+, and WBB6F1-/- mice were killed 2, 6, 12, and 24 hours after operation for measurement of VEGF by ELISA in systemic serum and peritoneal lavage fluid. Two further groups of CD-1 mice underwent AIS and received either a single perioperative dose of anti-VEGF monoclonal antibody (10 mug/mouse) or a similar volume of IgG isotypic antibody and adhesion formation 2 weeks later was evaluated.
  
  
  RESULTS
  WBB6F1-/- mice had less adhesions then did their WBB6F1+/+ counterparts (median [interquartile range] adhesion score 3[3-3] vs 1.5[1-2] respectively; P < .003). Local VEGF release peaked 6 hours after AIS in both WBB6F1+/+ and CD-1 mice whereas levels remained at baseline in WBB6F1-/- mice. CD-1 mice treated with a single dose of anti-VEGF therapy during operation had less adhesions than controls (2[1.25-2] vs 3[2.25-3], P = .0002).
  
  
  CONCLUSIONS
  Mast cells and VEGF are central to the formation of postoperative intra-abdominal adhesions with mast cells being responsible, either directly or indirectly, for VEGF release into the peritoneal cavity after operation. In tandem with the recent clinical success of anti-VEGF monoclonal antibodies in oncologic practice, our observations suggest an intriguing avenue for research and development of anti-adhesion strategy.
authors.affiliation: Department of Academic Surgery, Cork University Hospital, Ireland. rcahill@rcsi.ie
authors.forename: Ronan A
authors.initials: RA
authors.lastname: Cahill
authors.forename: Jiang Huai
authors.initials: JH
authors.lastname: Wang
authors.forename: Shastri
authors.initials: S
authors.lastname: Soohkai
authors.forename: H Paul
authors.initials: HP
authors.lastname: Redmond
mesh_terms: D000005:Abdomen / Q000601:surgery; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D007813:Laparotomy / Q000009:adverse effects; D008407:Mast Cells / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D010529:Peritoneal Cavity / Q000473:pathology / Q000503:physiopathology; D010532:Peritoneal Diseases / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D011183:Postoperative Complications / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D000267:Tissue Adhesions / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A