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Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation.
- Source :
-
Transplantation [Transplantation] 2003 Nov 15; Vol. 76 (9), pp. 1285-8. - Publication Year :
- 2003
-
Abstract
- Background: Islet-produced tissue factor (TF) triggers an adverse clotting reaction, the instant blood-mediated inflammatory reaction (IBMIR), providing a likely explanation for the need of tissue from multiple donors in clinical islet transplantation. In this study, the authors investigated whether compounds previously shown to affect TF and macrophage chemoattractant protein (MCP)-1 expression in monocytes and endothelial cells have the same effect in human islet cells.<br />Methods: Islets were cultured in the presence of l-arginine, cyclosporine A, enalapril, or nicotinamide for 48 hr, after which the TF content and MCP-1 expression were assessed. The effect of nicotinamide on IBMIR was evaluated by exposing the treated islets to fresh human ABO-compatible blood in an in vitro loop model.<br />Results: Nicotinamide was the only compound that significantly reduced both TF and MCP-1. This reduction was dose-dependent. The level of MCP-1 was strongly correlated with TF expression (r2=0.98). In addition, the level of TF was also correlated with the ability of the islets to initiate IBMIR (r2=0.94).<br />Conclusions: TF and MCP-1 expression in human islets can be decreased by adding nicotinamide to the culture medium. These observations indicate that the adverse effects of IBMIR in clinical islet transplantation could be reduced without endangering the recipient using antithrombotic drugs.
- Subjects :
- Arginine pharmacology
Cells, Cultured
Chemokine CCL2 metabolism
Cyclosporine pharmacology
Enalapril pharmacology
Gene Expression Regulation drug effects
Humans
Islets of Langerhans drug effects
Kinetics
Thromboplastin antagonists & inhibitors
Islets of Langerhans physiology
Islets of Langerhans Transplantation physiology
Niacinamide pharmacology
Thromboplastin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0041-1337
- Volume :
- 76
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- 14627904
- Full Text :
- https://doi.org/10.1097/01.TP.0000098905.86445.0F