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

Författare

  • Lisa Moberg
  • Annika Olsson
  • Christian Berne
  • Marie Felldin
  • Aksel Foss
  • Ragnar Källén
  • Kalja Salmela
  • Annika Tibell
  • Gunnar Tufveson
  • Bo Nilsson
  • Olle Korsgren

Summary, in English

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 (r(2)=0.98). In addition, the level of TF was also correlated with the ability of the islets to initiate IBMIR (r(2)=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.

Publiceringsår

2003

Språk

Engelska

Sidor

1285-1288

Publikation/Tidskrift/Serie

Transplantation

Volym

76

Issue

9

Dokumenttyp

Artikel i tidskrift

Förlag

Lippincott Williams & Wilkins

Ämne

  • Surgery

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1534-6080