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Article Dans Une Revue Transplantation Année : 2008

The role of macrophage migration inhibitory factor in mouse islet transplantation.

Christian Toso
  • Fonction : Auteur
Véronique Serre-Beinier
  • Fonction : Auteur
Juliet Emamaullee
  • Fonction : Auteur
Shaheed Merani
  • Fonction : Auteur
Mathieu Armanet
  • Fonction : Auteur
Domenico Bosco
  • Fonction : Auteur
Thierry Calandra
  • Fonction : Auteur
Thierry Roger
  • Fonction : Auteur
  • PersonId : 858693
Philippe Morel
  • Fonction : Auteur
a M James Shapiro
  • Fonction : Auteur
Thierry Berney
  • Fonction : Auteur

Résumé

BACKGROUND: Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced by many tissues including pancreatic beta-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 gamma 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.

Dates et versions

hal-00388734 , version 1 (27-05-2009)

Identifiants

Citer

Christian Toso, Véronique Serre-Beinier, Juliet Emamaullee, Shaheed Merani, Mathieu Armanet, et al.. The role of macrophage migration inhibitory factor in mouse islet transplantation.. Transplantation, 2008, 86 (10), pp.1361-9. ⟨10.1097/TP.0b013e31818bdbef⟩. ⟨hal-00388734⟩
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