Background. Data indicates that early xenoislet graft failure is due to non specific inflammatory mechanisms that occur prior to T cell mediated rejection. The host hepatic endothelial cell may be important in this process because it is essentially the first cellular barrier encountered by intraportally introduced islets. We have characterized the initial response of endothelium to xenogeneic islets by measuring the expression of 11-1alpha, TNF-alpha, IFN-gamma, and iNOS mRNA in an in vitro dog-to-pig model of xenoislet transplantation. / Materials & methods. Dog islets were co-cultured with either porcine hepatic endothelium or porcine aortic endothelium over a 24-hour period in serum free medium. RNA was extracted at eight time points. RT-PCR was performed in order to visualize II-1alpha, TNF-alpha, IFN-gamma, and BIOS expression. Bands were semiquantitated by comparison to an external standard (GAPDH) using band densitometry. / Results. Hepatic endothelium had early (one hour) expression of IL-1alpha, IFN-gamma, and iNOS transcript. IL-1alpha peaked at two hours, IFN-gamma at 12 hours, and iNOS at one and 12 hours. Aortic endothelium expressed low levels of IL-1alpha and TNF-alpha, but not IFN-gamma or NOS. / Conclusions. We have demonstrated that xenogeneic islets are able to activate host endothelial cells without serum or immune cells. The observed endothelial response corresponds with known islet toxic substances. Furthermore, the response differs between endothelial beds suggesting that these differences may be important in choosing suitable implantation sites for islets. Our findings suggest that host endothelium may play an important part in early injury of islet xenotransplants.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33851 |
| Date | January 2001 |
| Creators | Tan, Michael, 1970- |
| Contributors | Metrakos, Peter (advisor), Christou, Nicolas V. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Division of Surgical Research.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001862600, proquestno: MQ78968, Theses scanned by UMI/ProQuest. |
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