胆绿素
细胞保护
血红素加氧酶
血红素
再灌注损伤
微循环
移植
药理学
化学
免疫学
氧化应激
医学
细胞生物学
缺血
生物
生物化学
内科学
酶
作者
Masamichi Katori,Ronald W. Busuttil,Jerzy W. Kupiec‐Weglinski
出处
期刊:Transplantation
[Ovid Technologies (Wolters Kluwer)]
日期:2002-10-01
卷期号:74 (7): 905-912
被引量:191
标识
DOI:10.1097/00007890-200210150-00001
摘要
The heme oxygenase-1 (HO-1) system, the rate-limiting step in the conversion of heme, is among the most critical of cytoprotective mechanisms activated during cellular stress. The cytoprotection may result from the elimination of heme and the function of HO-1 downstream mediators, that is, biliverdin, carbon monoxide, and free iron. HO-1 overexpression exerts beneficial effects in a number of transplantation models, including antigen-independent ischemia/reperfusion injury, acute and chronic allograft rejection, and xenotransplantation. The HO-1 system is thought to exert four major functions: (1) antioxidant function; (2) maintenance of microcirculation; (3) modulatory function upon the cell cycle; and (4) anti-inflammatory function. The antioxidant function depends on heme degradation, oxygen consumption, biliverdin, and production of ferritin via iron accumulation. The production of carbon monoxide, which has vasodilation and antiplatelet aggregation properties, maintains tissue microcirculation and may be instrumental in antiapoptotic and cell arrest mechanisms. Heme catabolism and HO-1 overexpression exert profound direct and indirect inhibitory effects on the cascade of host inflammatory responses mediated by neutrophils, macrophages, and lymphocytes. These anti-inflammatory properties result in cytoprotection in a broad spectrum of graft injury experimental models, including ischemia/reperfusion, acute and chronic allograft, and xenotransplant rejection. Further, the multifaceted targets of HO-1–mediated cytoprotection may simultaneously benefit both local graft function and host systemic immune responses. Thus, the HO-1 system serves as a novel therapeutic concept in organ transplantation.
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