Project 03
Mechanism of harvesting injury in the intestinal muscularis and impact on small bowel transplantation
Study group Schäfer/Türler
Department of Surgery
Sigmund-Freud-Str. 25 l 53105 Bonn
The activation and bi-directional migration of leukocytes between the donor and the recipient plays a crucial role in the development of organ rejection in small bowel transplantation.
It has been demonstrated that the intestinal muscularis hosts a dense network of resident macrophages. Any kind of trauma or insult results in the rapid activation of these resident macrophages followed by a cellular inflammatory reaction with leukocyte recruitment. The potential impact of this mechanism on the success of small bowel transplantation has been neglected until now. We have recently shown in a prospective human study on small bowel transplantation that inflammatory events in the intestinal muscularis are already occurring during the early phase of organ harvest and possible stimuli for this early initiation could be surgical manipulation during organ harvest. This means that the inflammatory milieu is already evident before the onset of immunological interactions between the recipient and the graft during the reperfusion period. We hypothesize, that the inflammatory events within the intestinal muscularis promote immunological complications in small bowel transplantation and that an inhibition of the inflammatory cascade before or during organ harvest might improve the clinical outcome of small bowel transplantation.
The goals of the research project are 1. to verify and delineate the inflammatory events within the intestinal muscularis during organ harvest and transplantation, 2. to define the impact of these inflammatory events on organ rejection and 3. to determine the effect of anti-inflammatory donor-pretreatment on the outcome of small bowel transplantation.