Variable efficacy of N6-(1-iminoethyl)-L-lysine in acute cardiac transplant rejection.
Variable efficacy of N6-(1-iminoethyl)-L-lysine in acute cardiac transplant rejection.
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N6-(1-亚氨基乙基)-L-赖氨酸在急性心脏移植排斥反应中的不同功效。
DOI：
10.1152/ajpheart.00356.2003
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Adams,MarkB
中科院分区：
文献类型：
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作者：
Pieper,GalenM;Nilakantan,Vani;Hilton,Gail;Zhou,Xianghua;Khanna,AshwaniK;Halligan,NadineLN;Felix,ChristopherC;Kampalath,Bal;Griffith,OwenW;Hayward,MikeA;Roza,AllanM;Adams,MarkB
我们研究了n6 -（1-亚氨基乙基）-l-赖氨酸（l-NIL）对急性心脏移植排斥反应的疗效和作用机制，n6 -（1-亚氨基乙基）-l-赖氨酸（l-NIL）是一种高选择性的诱导性一氧化氮合成酶（iNOS）抑制剂。l-NIL在不改变iNOS蛋白水平的情况下产生血浆NO副产物的浓度依赖性衰减和血红素蛋白亚硝基化的降低。术后第4天，l-NIL未改变转录因子核因子-κB和激活蛋白-1结合活性的升高。而il - nil可降低炎症细胞浸润，仅在1.0 μg/ml剂量下延长移植物存活，但不完全阻断NO的产生。高浓度的il - nil（30和60 μg/ml）消除了增加的NO产生，但未能改善移植物存活，甚至增强了NF-κB结合活性。干扰素-γ、白细胞介素-6和白细胞介素-10的细胞因子基因表达增加表明同种免疫激活仅在1.0 μg/ml - nil处理下被抑制。这些发现提示一氧化氮在急性同种异体心脏移植排斥反应中的复杂作用。部分抑制iNOS有利于移植物存活，而完全消融可能不利于移植物存活。这些研究对理解一氧化氮在急性排斥反应中的双重作用具有重要意义，并有助于调和文献中的差异。
We examined the efficacy and mechanism of action ofN6-(1-iminoethyl)-l-lysine (l-NIL), a highly selective inhibitor of inducible nitric oxide (NO) synthase (iNOS), on acute cardiac transplant rejection.l-NIL produced a concentration-dependent attenuation of plasma NO by-products and a decrease in nitrosylation of heme protein without altering protein levels of iNOS. At postoperativeday 4,l-NIL did not alter the increased binding activities for transcription factors nuclear factor-κB and activator protein-1. Whereasl-NIL decreased inflammatory cell infiltration, graft survival was only prolonged at the dose of 1.0 μg/ml that incompletely blocked NO production. Higherl-NIL concentrations (30 and 60 μg/ml) ablated the increased NO production but failed to improve graft survival and even potentiated NF-κB binding activity examined atday 6. Alloimmune activation indicated by increased cytokine gene expression for interferon-γ, interleukin-6, and interleukin-10 was inhibited in grafts only by treatment with 1.0 μg/mll-NIL. These findings suggest a complex role of NO in acute cardiac allograft rejection. Partial inhibition of iNOS is beneficial to graft survival, whereas total ablation may oppose any benefits to graft survival. These studies have important implications in understanding the dual role of NO in acute rejection and help to reconcile discrepancies in the literature.