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The role of macrophage migration inhibitory factor in mouse islet transplantation

Serre-Beinier, Veronique
Emamaullee, Juliet
Merani, Shaheed
Calandra, Thierry
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Published in Transplantation. 2008, vol. 86, no. 10, p. 1361-1369
Abstract 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.
Keywords AnimalsApoptosisBlood Glucose/metabolismCrosses, GeneticDiabetes Mellitus, Experimental/blood/surgeryGraft Rejection/geneticsGraft Survival/geneticsInflammationIntramolecular Oxidoreductases/deficiency/genetics/*physiologyIslets of Langerhans Transplantation/immunology/pathology/*physiologyMacrophage ActivationMacrophage Migration-Inhibitory Factors/deficiency/genetics/*physiologyMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutTreatment Outcome
PMID: 19034004
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Research groups Chirurgie viscérale (104)
Chirurgie viscérale (HUG)
La transplantation d'îlots de Langerhans (623)
Transplantation et hépatologie (905)
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TOSO, Christian et al. The role of macrophage migration inhibitory factor in mouse islet transplantation. In: Transplantation, 2008, vol. 86, n° 10, p. 1361-1369. doi: 10.1097/TP.0b013e31818bdbef https://archive-ouverte.unige.ch/unige:19226

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Deposited on : 2012-03-27

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