Application of carbon monoxide for transplantation

Carbon monoxide (CO) is an invisible, chemically inert, colorless and odorless gas and is toxic at high concentrations due to its interference with oxygen delivery. However, CO is endogenously and physiologically generated in mammalian cells via the catabolism of heme in a rate-limiting step of heme oxygenase systems, and CO potently protects against cellular injury. CO relaxes blood vessels and exerts anti-thrombotic effects by inhibiting platelet aggregation and derepressing fibrinolysis. In addition, CO reduces ischemia/reperfusion injury and inflammatory responses. CO inhibits apoptosis of endothelial and epithelial cells and reduces proliferation of smooth muscle cells, fibroblasts and T lymphocytes. Thus, there is accumulating evidence to support the notion that CO treatment of transplant donors, organs, or recipients can prevent graft dysfunction due to rejection or ischemia/reperfusion injury. This invited review discusses recent advances and current knowledge pertaining to CO research in the field of transplantation. In addition, we will discuss the clinical applicability of CO as a promising therapeutic strategy for the treatment of transplant patients.