TY - JOUR
T1 - A novel strategy against ischemia and reperfusion injury
T2 - Cytoprotection with heme oxygenase system
AU - Katori, Masamichi
AU - Anselmo, Dean M.
AU - Busuttil, Ronald W.
AU - Kupiec-Weglinski, Jerzy W.
N1 - Funding Information:
Supported by NIH Grants RO1 AI42223 and RO1 AI23847, a UCLA BioStar grant, and by The Dumont Research Foundation.
PY - 2002/5
Y1 - 2002/5
N2 - Much interest has recently been focused on the physiological/pathological role of the heme oxygenase (HO) system, the rate-limiting step in the conversion of heme, in inflammatory events. The HO system may be instrumental in mediating a number of cytoprotective effects, because of its end products, biliverdin, carbon monoxide (CO) and ferrous free iron (Fe2+). As each of the byproducts acts dependently and/or co-operatively with each other, their in vivo effects are complex. In general, the HO system is thought to exert three major functions in ischemia/reperfusion injury: (1) anti-oxidant effects; (2) maintenance of microcirculation; and (3) modulatory effects upon the cell cycle. The anti-oxidant functions depend on heme degradation, oxygen consumption and the production of biliverdin/ferritin via iron accumulation. On the other hand, the production of CO, which has vasodilatory and anti-platelet aggregative properties, can maintain tissue microcirculation. Strikingly, CO may also be instrumental in anti-apoptotic and cell arrest mechanisms. The HO system prevents early injury in the re-perfused organ, and inhibits the function of immune reactive cells, such as neutrophils, macrophages and lymphocytes. The role of the HO system as a novel strategy to mitigate an antigen-independent ischemia/reperfusion injury has been documented in a number of transplantation models.
AB - Much interest has recently been focused on the physiological/pathological role of the heme oxygenase (HO) system, the rate-limiting step in the conversion of heme, in inflammatory events. The HO system may be instrumental in mediating a number of cytoprotective effects, because of its end products, biliverdin, carbon monoxide (CO) and ferrous free iron (Fe2+). As each of the byproducts acts dependently and/or co-operatively with each other, their in vivo effects are complex. In general, the HO system is thought to exert three major functions in ischemia/reperfusion injury: (1) anti-oxidant effects; (2) maintenance of microcirculation; and (3) modulatory effects upon the cell cycle. The anti-oxidant functions depend on heme degradation, oxygen consumption and the production of biliverdin/ferritin via iron accumulation. On the other hand, the production of CO, which has vasodilatory and anti-platelet aggregative properties, can maintain tissue microcirculation. Strikingly, CO may also be instrumental in anti-apoptotic and cell arrest mechanisms. The HO system prevents early injury in the re-perfused organ, and inhibits the function of immune reactive cells, such as neutrophils, macrophages and lymphocytes. The role of the HO system as a novel strategy to mitigate an antigen-independent ischemia/reperfusion injury has been documented in a number of transplantation models.
KW - Anti-oxidant
KW - Heme oxygenase
KW - Ischemia/reperfusion injury
KW - Oxygen radical formation
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U2 - 10.1016/S0966-3274(02)00043-6
DO - 10.1016/S0966-3274(02)00043-6
M3 - Article
C2 - 12180835
AN - SCOPUS:0036580337
SN - 0966-3274
VL - 9
SP - 227
EP - 233
JO - Transplant Immunology
JF - Transplant Immunology
IS - 2-4
ER -