title: Nicotinamide inhibits tissue factor expression in isolated human pancreatic islets: implications for clinical islet transplantation.
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.
  
  
  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.
authors: Department of Radiology, Oncology, and Clinical Immunology, Division of Clinical Immunology, The Rudbeck Laboratory, University Hospital, Uppsala, Sweden. lisa.moberg@klinimm.uu.se
authors: Lisa
authors: L
authors: Moberg
authors: Annika
authors: A
authors: Olsson
authors: Christian
authors: C
authors: Berne
authors: Marie
authors: M
authors: Felldin
authors: Aksel
authors: A
authors: Foss
authors: Ragnar
authors: R
authors: Källen
authors: Kaija
authors: K
authors: Salmela
authors: Annika
authors: A
authors: Tibell
authors: Gunnar
authors: G
authors: Tufveson
authors: Bo
authors: B
authors: Nilsson
authors: Olle
authors: O
authors: Korsgren
mesh_terms: 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*
chemical_list: D018932:Chemokine CCL2; D009536:Niacinamide; D004656:Enalapril; D016572:Cyclosporine; D013925:Thromboplastin; D001120:Arginine