Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species

  • Tocco G
  • Illigens B
  • Malfroy B
 et al. 
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Abstract

We tested the effects of salen manganese (Salen-Mn) complexes, which are scavengers of reactive oxygen species exhibiting superoxide dismutase and catalase activities on the rejection of and alloresponse to fully allogeneic skin grafts in mice. We showed that pre-transplant treatment of C57Bl/6 donor skin or of BALB/c recipients with Salen-Mn complexes significantly delayed allograft rejection. ELISPOT analysis of alloimmune response of treated mice revealed a significant reduction of the frequency of type 1 cytokine (pro-inflammatory) producing T-cells, while the number of activated T-cells producing type 2 cytokines was elevated. In addition, anti-oxidative treatment of graft recipients resulted in a profound inhibition of their donor-specific cytotoxic T-cell response. Our results indicate that salen manganese complexes mediate their effect on graft rejection both by reducing the susceptibility of graft tissue to ROS-mediated injury and by exerting an anti-inflammatory effect in recipients. © 2006.

Author-supplied keywords

  • Allotransplantation
  • Cytokines
  • Reactive oxygen species
  • Skin graft
  • T-cells

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Authors

  • Georges Tocco

  • Ben M.W. Illigens

  • Bernard Malfroy

  • Gilles Benichou

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