title: The role of macrophage migration inhibitory factor in mouse islet transplantation.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Islet Transplant Program, Alberta Diabetes Institute, University of Alberta, Edmonton AB, Canada. Christian.toso@hcuge.ch
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.forename: Véronique
authors.initials: V
authors.lastname: Serre-Beinier
authors.forename: Juliet
authors.initials: J
authors.lastname: Emamaullee
authors.forename: Shaheed
authors.initials: S
authors.lastname: Merani
authors.forename: Mathieu
authors.initials: M
authors.lastname: Armanet
authors.forename: Anne
authors.initials: A
authors.lastname: Wojtusciszyn
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
authors.forename: Thierry
authors.initials: T
authors.lastname: Calandra
authors.forename: Thierry
authors.initials: T
authors.lastname: Roger
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D003433:Crosses, Genetic; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery; D006084:Graft Rejection / Q000235:genetics; D006085:Graft Survival / Q000235:genetics; D007249:Inflammation; D019746:Intramolecular Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008262:Macrophage Activation; D008263:Macrophage Migration-Inhibitory Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C076231:Mif protein, mouse