The role of macrophage migration inhibitory factor in mouse islet transplantation

Christian Toso, Véronique Serre-Beinier, Juliet Emamaullee, Shaheed Merani, Mathieu Armanet, Anne Wojtusciszyn, Domenico Bosco, Thierry Calandra, Thierry Roger, Philippe Morel, A. M.James Shapiro, Thierry Berney

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

BACKGROUND.: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by many tissues including pancreatic β-cells. METHODS.: This study investigates the impact of MIF on islet transplantation using MIF knock-out (MIFko) mice. RESULTS.: Early islet function, assessed with a syngeneic marginal islet mass transplant model, was enhanced when using MIFko islets (P<0.05 compared with wild-type [WT] controls). This result was supported by increased in vitro resistance of MIFko islets to apoptosis (terminal deoxynucleotide tranferase-mediated dUTP nick-end labeling assay), and by improved glucose metabolism (lower blood glucose levels, reduced glucose areas under curve and higher insulin release during intraperitoneal glucose challenges, and in vitro in the absence of MIF, P<0.01). The beneficial impact of MIFko islets was insufficient to delay allogeneic islet rejection. However, the rejection of WT islet allografts was marginally delayed in MIFko recipients by 6 days when compared with WT recipient (P<0.05). This effect is supported by the lower activity of MIF-deficient macrophages, assessed in vitro and in vivo by cotransplantation of islet/macrophages. Leukocyte infiltration of the graft and donor-specific lymphocyte activity (mixed lymphocyte reaction, interferon γ ELISPOT) were similar in both groups. CONCLUSION.: These data indicate that targeting MIF has the potential to improve early function after syngeneic islet transplantation, but has only a marginal impact on allogeneic rejection.

Original languageEnglish (US)
Pages (from-to)1361-1369
Number of pages9
JournalTransplantation
Volume86
Issue number10
DOIs
StatePublished - Nov 27 2008
Externally publishedYes

Keywords

  • Cytokine
  • Islet
  • Macrophage
  • Transplantation.

ASJC Scopus subject areas

  • Transplantation

Fingerprint

Dive into the research topics of 'The role of macrophage migration inhibitory factor in mouse islet transplantation'. Together they form a unique fingerprint.

Cite this