Basic ResearchMolecular and functional observations on the donor intestinal muscularis during human small bowel transplantation☆,☆☆
Section snippets
Patients and small bowel specimens
Adult patients undergoing small intestinal transplantation at the University of Pittsburgh were prospectively included in the study. Specimens were obtained during back table preparation of the donor graft and intraoperatively during graft implantation from patients undergoing small intestinal transplantation. Intestinal segments (1.5-cm length) were removed from the aboral graft border at the end of the cold preservation period after the cumulative insult of harvesting (2.8 ± 0.2 hours between
Molecular inflammatory events
Gene expression analysis focused on the multifunctional cytokine IL-6, on MCP-1, and ICAM-1 as regulators of cellular inflammation, and on COX-2 as a kinetically active mediator. Real-time reverse-transcription PCR analysis showed a significant successive up-regulation in the messenger RNA (mRNA) values of all these mediators as the transplant procedure progressed: preserved donor grafts, before reperfusion of the implanted graft, and after reperfusion (Figures 1 and 2).
Discussion
Our results show that the human donor intestinal muscularis itself is an immunologically active participant in the development of a complex inflammatory response during the transplantation process. Additionally, that these local molecular events functionally result in the recruitment of circulating host leukocytes, a suppression in intestinal smooth muscle contractility, and a dysfunction in neuromuscular transmission.
We have shown that the intestinal muscularis of mammals is populated with a
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Address requests for reprints to: Anthony J. Bauer, Ph.D., Department of Medicine/Gastroenterology, University of Pittsburgh Medical School, S849 Scaife Hall, 3550 Terrace Street, Pittsburgh, Pennsylvania 15261.e-mail: [email protected]; fax: (412) 648-9731.
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Supported by National Institute of Health grants R01-GM-58241 and P50-GM-53789 and a grant from the Deutsche Forschungsgemeinschaft (TU 116/2-1).