Article

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

Cellular and Molecular Immunology Laboratory, Massachusetts General Hospital, Department of Surgery, Transplantation Unit, Harvard Medical School, Boston, MA, USA.
Cellular Immunology (impact factor: 1.97). 07/2006; 241(2):59-65. DOI:10.1016/j.cellimm.2006.06.009
Source: PubMed

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.

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Keywords

activated T-cells
 
allogeneic skin grafts
 
allograft rejection
 
anti-inflammatory effect
 
C57Bl/6 donor skin
 
catalase activities
 
donor-specific cytotoxic T-cell response
 
graft recipients
 
graft rejection
 
graft tissue
 
pre-transplant treatment
 
reactive oxygen species
 
salen manganese
 
salen manganese complexes
 
Salen-Mn
 
Salen-Mn complexes
 
superoxide dismutase
 
T-cells
 
type 1 cytokine
 
type 2 cytokines