Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.
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Affiliation
Department of Academic Surgery, Cork University Hospital, Ireland., rcahill@rcsi.ieIssue Date
2012-02-03T15:04:49ZMeSH
Abdomen/surgeryAnimals
Disease Models, Animal
Humans
Inflammation Mediators/physiology
Laparotomy/adverse effects
Mast Cells/*physiology
Mice
Mice, Knockout
Neovascularization, Pathologic/etiology/physiopathology/prevention & control
Peritoneal Cavity/pathology/physiopathology
Peritoneal Diseases/*etiology/physiopathology/prevention & control
Postoperative Complications/*etiology/physiopathology/prevention & control
Tissue Adhesions/*etiology/physiopathology/prevention & control
Vascular Endothelial Growth Factor A/antagonists & inhibitors/*secretion
Metadata
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Surgery. 2006 Jul;140(1):108-12.Journal
SurgeryDOI
10.1016/j.surg.2006.01.020PubMed ID
16857448Abstract
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.Language
engISSN
0039-6060 (Print)0039-6060 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1016/j.surg.2006.01.020