Journal
TRANSPLANTATION
Volume 86, Issue 10, Pages 1361-1369Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31818bdbef
Keywords
Cytokine; Macrophage; Islet; Transplantation
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Funding
- Geneva University Hospitals
- Swiss National Science Foundation [102134, 310000-118266]
- Swiss National Science Foundation
- Alberta Heritage Foundation for Medical Research (AHFMR)
- Rhind Foundation
- Leenaards and the Santos-Suarez Foundations
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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/macro-phages. 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.
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