Prolongation of alloskin graft survival by catalytic scavengers of reactive oxygen species.
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.
Tocco
Georges
G
Cellular and Molecular Immunology Laboratory, Massachusetts General Hospital, Department of Surgery, Transplantation Unit, Harvard Medical School, Boston, MA, USA.
Illigens
Ben M-W
BM
Malfroy
Bernard
B
Benichou
Gilles
G
D000818:Animals; D002374:Catalase / Q000378:metabolism; D002384:Catalysis / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000187:drug effects* / Q000276:immunology*; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000276:immunology; D008345:Manganese / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D017382:Reactive Oxygen Species / Q000378:metabolism*; D016038:Skin Transplantation / Q000276:immunology*; D013482:Superoxide Dismutase / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014184:Transplantation, Homologous
D016207:Cytokines; D016166:Free Radical Scavengers; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D008345:Manganese; D002374:Catalase; D013482:Superoxide Dismutase