Katori Masamichi, Anselmo Dean M, Busuttil Ronald W, Kupiec-Weglinski Jerzy W
Dumont-UCLA Transplant Center, Division of Liver and Pancreas Transplantation, Los Angeles, CA 90095, USA.
Transpl Immunol. 2002 May;9(2-4):227-33. doi: 10.1016/s0966-3274(02)00043-6.
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.
近期，血红素加氧酶（HO）系统作为血红素转化的限速步骤，在炎症事件中的生理/病理作用备受关注。HO系统可能有助于介导多种细胞保护作用，这归因于其终产物胆绿素、一氧化碳（CO）和亚铁离子（Fe2+）。由于每种副产物相互独立和/或协同发挥作用，它们在体内的作用较为复杂。一般来说，HO系统在缺血/再灌注损伤中被认为发挥三种主要功能：（1）抗氧化作用；（2）维持微循环；（3）对细胞周期的调节作用。抗氧化功能依赖于血红素降解、耗氧以及通过铁积累产生胆绿素/铁蛋白。另一方面，具有血管舒张和抗血小板聚集特性的CO的产生可维持组织微循环。引人注目的是，CO在抗凋亡和细胞停滞机制中也可能发挥作用。HO系统可预防再灌注器官的早期损伤，并抑制免疫反应性细胞如中性粒细胞、巨噬细胞和淋巴细胞的功能。HO系统作为减轻非抗原依赖性缺血/再灌注损伤的一种新策略，已在多个移植模型中得到证实。
