Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.

Hdl Handle:
http://hdl.handle.net/10147/208832
Title:
Mast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.
Authors:
Cahill, Ronan A; Wang, Jiang Huai; Soohkai, Shastri; Redmond, H Paul
Affiliation:
Department of Academic Surgery, Cork University Hospital, Ireland., rcahill@rcsi.ie
Citation:
Surgery. 2006 Jul;140(1):108-12.
Journal:
Surgery
Issue Date:
3-Feb-2012
URI:
http://hdl.handle.net/10147/208832
DOI:
10.1016/j.surg.2006.01.020
PubMed ID:
16857448
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.
Language:
eng
MeSH:
Abdomen/surgery; Animals; 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
ISSN:
0039-6060 (Print); 0039-6060 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorCahill, Ronan Aen_GB
dc.contributor.authorWang, Jiang Huaien_GB
dc.contributor.authorSoohkai, Shastrien_GB
dc.contributor.authorRedmond, H Paulen_GB
dc.date.accessioned2012-02-03T15:04:49Z-
dc.date.available2012-02-03T15:04:49Z-
dc.date.issued2012-02-03T15:04:49Z-
dc.identifier.citationSurgery. 2006 Jul;140(1):108-12.en_GB
dc.identifier.issn0039-6060 (Print)en_GB
dc.identifier.issn0039-6060 (Linking)en_GB
dc.identifier.pmid16857448en_GB
dc.identifier.doi10.1016/j.surg.2006.01.020en_GB
dc.identifier.urihttp://hdl.handle.net/10147/208832-
dc.description.abstractBACKGROUND: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAbdomen/surgeryen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshDisease Models, Animalen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInflammation Mediators/physiologyen_GB
dc.subject.meshLaparotomy/adverse effectsen_GB
dc.subject.meshMast Cells/*physiologyen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Knockouten_GB
dc.subject.meshNeovascularization, Pathologic/etiology/physiopathology/prevention & controlen_GB
dc.subject.meshPeritoneal Cavity/pathology/physiopathologyen_GB
dc.subject.meshPeritoneal Diseases/*etiology/physiopathology/prevention & controlen_GB
dc.subject.meshPostoperative Complications/*etiology/physiopathology/prevention & controlen_GB
dc.subject.meshTissue Adhesions/*etiology/physiopathology/prevention & controlen_GB
dc.subject.meshVascular Endothelial Growth Factor A/antagonists & inhibitors/*secretionen_GB
dc.titleMast cells facilitate local VEGF release as an early event in the pathogenesis of postoperative peritoneal adhesions.en_GB
dc.contributor.departmentDepartment of Academic Surgery, Cork University Hospital, Ireland., rcahill@rcsi.ieen_GB
dc.identifier.journalSurgeryen_GB
dc.description.provinceMunster-

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