Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts
Top Cited Papers
- 22 February 2005
- journal article
- review article
- Published by Oxford University Press (OUP) in Journal of Leukocyte Biology
- Vol. 77 (5), 587-597
- https://doi.org/10.1189/jlb.1104649
Abstract
Recent advances in clinical protocols have improved the outcomes of pancreatic islet transplantation (PIT), yet PIT recipients typically require pancreatic islet grafts derived from multiple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involvement of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1β appears to be among the most important inflammatory mediators, causing pancreatic islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer cells improves outcomes following experimental PIT. Imediately after transplantation, the pancreatic islets are perfused only by portal vein blood until the process of angiogenesis restores arterial blood flow some 7–10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion molecules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the immediate post-transplant period, hepatocytes may contribute to pancreatic islet injury through the production of NO. This paper reviews literature regarding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic ischemia-reperfusion and their relation to the survival and function of intrahepatic pancreatic islet grafts.Keywords
This publication has 96 references indexed in Scilit:
- Heme oxygenase-1 fused to a TAT peptide transduces and protects pancreatic β-cellsBiochemical and Biophysical Research Communications, 2003
- Insulin Independence Following Isolated Islet Transplantation and Single Islet InfusionsAnnals of Surgery, 2003
- Prevention of autoimmune diabetes in NOD mice by troglitazone is associated with modulation of ICAM-1 expression on pancreatic islet cells and IFN-γ expression in splenic T cellsBiochemical and Biophysical Research Communications, 2003
- Achievement of insulin independence in three consecutive type-1 diabetic patients via pancreatic islet transplantation using islets isolated at a remote islet isolation centerTransplantation, 2002
- Pancreatic β Cell–specific Expression of Thioredoxin, an Antioxidative and Antiapoptotic Protein, Prevents Autoimmune and Streptozotocin-induced DiabetesThe Journal of Experimental Medicine, 1998
- Prostaglandin synthase 2Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1996
- THE ROLE OF NITRIC OXIDE IN IL-1β-MEDIATED DYSFUNCTION OF RODENT ISLETS OF LANGERHANSTransplantation, 1994
- Hepatic arterial and portal venous oxygen content and extraction in liver cirrhosisLiver International, 1993
- Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat.JCI Insight, 1990
- CYTOKINE-INDUCED PROCOAGULANT ACTIVITY IN MONOCYTES AND ENDOTHELIAL CELLS FURTHER ENHANCEMENT BY CYCLOSPORINETransplantation, 1988