Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation.
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.


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.


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).


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.
Moberg
Lisa
L
Department of Radiology, Oncology, and Clinical Immunology, Division of Clinical Immunology, The Rudbeck Laboratory, University Hospital, Uppsala, Sweden. lisa.moberg@klinimm.uu.se
Olsson
Annika
A
Berne
Christian
C
Felldin
Marie
M
Foss
Aksel
A
Källen
Ragnar
R
Salmela
Kaija
K
Tibell
Annika
A
Tufveson
Gunnar
G
Nilsson
Bo
B
Korsgren
Olle
O
D001120:Arginine / Q000494:pharmacology; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000502:physiology*; D007700:Kinetics; D009536:Niacinamide / Q000494:pharmacology*; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000378:metabolism*
D018932:Chemokine CCL2; D009536:Niacinamide; D004656:Enalapril; D016572:Cyclosporine; D013925:Thromboplastin; D001120:Arginine