Protection of Grafts by Hemoxygenase‐1 and its Toxic Product Carbon Monoxide

Abstract

The optimization of immunosuppressive therapies resulted inthe establishment of organ transplantation as long-term ther-apy of many end-stage diseases. However, late graft dys-function and loss, in particular, are still major problems. Fur-thermore, with an increasing demand for transplantation,suboptimal grafts are increasingly used for transplantation. Inthose grafts alloantigen-independent events that cannot beinhibited by established immunosuppressive therapies maybe particularly detrimental. The impact of alloantigen-inde-pendent factors on long-term graft survival is exemplifiedbest by the improved survival of grafts from living donors. Inaddition, it has become increasingly obvious that alloantigen-independent events resulting in tissue stress and injury maynot only delay early graft function, but are also associatedwith impaired graft function and survival in the long term (1).One explanation for this phenomenon may be that unspecificinflammatory intragraft events trigger antigen-presentingcells and endothelial cells, resulting in increased alloantigen-dependent immune processes.