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Title: Trafficking of monocytes to the peritoneum after abdominal surgery and their role in the development of septic complications
Author: Bunker, Nicholas
ISNI:       0000 0005 0732 0004
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2014
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Background Peritoneal infection that follows surgery is associated with SIRS and the development of multi-organ dysfunction. It has a high mortality. The dynamics of leucocyte trafficking into the peritoneal cavity and the expression of cytokines in response to either endotoxin or abdominal surgery will effect the development of both local and systemic inflammation. Firstly the leucocyte trafficking in response to intraperitoneal LPS (lipopolysaccharide) is compared to an abdominal incision. Then, using the expression of TNFα on the cell membrane as a marker of pro-inflammatory status, this expression is described in animals undergoing surgery followed by a 'second hit' of ip LPS. Finally the ability of these trafficked cells to trigger SIRS leading to pathophysiological effects in the lungs was assessed. Methods C57/B6 mice were exposed to either an intra-peritoneal dose of 20ng LPS or abdominal surgery and the leucocytes identified and counted in both blood and peritoneal lavage fluid by flow cytometry. A two-hit model was devised, abdominal surgery the primary hit and 24 hours later ip LPS the second hit. The expression of TNFα was measured with flow cytometry. Using two intravenous dyes a lung permeability index was created comparing mice primed by surgery and those just receiving LPS. The data was analysed using student t-test and one-way ANOVA as appropriate. Results: The time course of migration was different for the various leucocyte sub-populations in response to both LPS and surgery. There was a significant increase in the expression of membrane bound TNFα on monocytes and macrophages in the two-hit model than with surgery or LPS alone. There was a trend to greater lung permeability in the two-hit group. Conclusions Leucocytes migrate to the peritoneal cavity after surgery and are primed to respond vigorously to a subsequent dose of LPS. This may have effects on lung permeability.
Supervisor: Handy, Jonathan; O'Dea, Kieran; Takata, Masao Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral