Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.
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.
Cahill
Ronan A
RA
Department of Academic Surgery, Cork University Hospital, Ireland. rcahill@rcsi.ie
Wang
Jiang Huai
JH
Soohkai
Shastri
S
Redmond
H Paul
HP
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*
D018836:Inflammation Mediators; D042461:Vascular Endothelial Growth Factor A