DcR3/TR6 effectively prevents islet primary nonfunction after transplantation.

Détails

ID Serval
serval:BIB_854D5CAB2E54
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
DcR3/TR6 effectively prevents islet primary nonfunction after transplantation.
Périodique
Diabetes
Auteur(s)
Wu Y., Han B., Luo H., Roduit R., Salcedo T.W., Moore P.A., Zhang J., Wu J.
ISSN
0012-1797 (Print)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
09/2003
Peer-reviewed
Oui
Volume
52
Numéro
9
Pages
2279-2286
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Islet primary nonfunction (PNF) is defined as the loss of islet function after transplantation for reasons other than graft rejection. It is a major obstacle to successful and efficient islet transplantation. DcR3/TR6 is a soluble death decoy receptor belonging to the tumor necrosis factor (TNF) receptor family, and it can block apoptosis mediated by several TNF receptor family members such as Fas and LT beta R. In this study, we used TR6 to protect islets from PNF after transplantation. Untreated isogeneic or allogeneic islet transplantation had PNF incidence of 25 and 26.5%, respectively. Administration of TR6 totally prevented PNF in allogeneic islet transplantation. In vitro experiments showed an increased apoptosis among islets that were treated with FasL and gamma-interferon (IFN-gamma) in combination. TR6 significantly reduced such apoptosis. Functional study showed that insulin release was compromised after FasL and IFN-gamma treatment, and the compromise could be prevented with TR6-Fc. This indicates that TR6 indeed protected beta-cells from damage caused by FasL and IFN-gamma. Further in vivo experiments showed that syngeneic islet transplantation between lpr/lpr and gld/gld mice was significantly more efficacious than that conducted between wild-type mice. These results suggest that Fas-mediated apoptosis plays an important role in PNF, and use of TR6 may be a novel strategy to prevent PNF in clinical islet transplantation.

Mots-clé
Animals, Antigens, CD95/metabolism, Antineoplastic Agents/pharmacology, Apoptosis/drug effects, Cells, Cultured, Fas Ligand Protein, Graft Survival/drug effects, Humans, Interferon-gamma/pharmacology, Islets of Langerhans/drug effects, Islets of Langerhans/physiology, Islets of Langerhans Transplantation, Membrane Glycoproteins/metabolism, Membrane Glycoproteins/pharmacology, Mice, Mice, Inbred C57BL, Receptors, Cell Surface, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Member 6b
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/09/2017 13:13
Dernière modification de la notice
08/05/2019 21:22
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