Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplantation.
Extended cold preservation of the graft liver enhances neutrophil-mediated pulmonary injury after liver transplantation.
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发表时间：
2005-07
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通讯作者：
H. Shimizu;M. Kataoka;M. Ohtsuka;Hiroshi Ito;F. Kimura;A. Togawa;H. Yoshidome;A. Kato;M. Miyazaki
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作者：
H. Shimizu;M. Kataoka;M. Ohtsuka;Hiroshi Ito;F. Kimura;A. Togawa;H. Yoshidome;A. Kato;M. Miyazaki
背景/目的肝移植后肺损伤的确切机制，特别是与冷缺血时间相关的机制尚不清楚。方法观察不同冷缺血时间(4℃威斯康星大学液中1、6和24小时)肝移植后肺内中性粒细胞(PMN)的积聚和肺损伤的组织学变化。用定量逆转录聚合酶链式反应检测肺组织细胞因子诱导的中性粒细胞趋化因子(CINC)和巨噬细胞炎性蛋白-2(MIP-2)的表达。肝移植后，刺激这些趋化因子产生的肿瘤坏死因子-α(TNFpha)水平也被监测。结果再灌流3h后，冷缺血24小时组肺组织中性粒细胞计数和肺水肿量均显著高于冷缺血1小时组和冷缺血6小时组。24小时组肺组织MIP-2和CINC mRNA表达均显著上调。组织学检查，24小时组肺损伤明显，以肺间质水肿、肺泡出血为特征。此外，仅在24小时组检测到肝静脉内的肿瘤坏死因子。结论冷缺血时间延长通过肝源性肿瘤坏死因子α上调肺组织MIP-2和CINC的表达，促进PMN聚集，导致肝移植后肺损伤加重。
BACKGROUND/AIMS The precise mechanisms of pulmonary injury after liver transplantation, especially those associated with cold ischemia time, are not yet clear. METHODOLOGY We histologically evaluated the number of accumulated polymorphonuclear neutrophils (PMNs) in lungs, and pulmonary injury after liver transplantation with varying periods of cold ischemia (1, 6 and 24h in University of Wisconsin solution at 4 degrees C). Pulmonary expression of cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein-2 (MIP-2) mRNA were investigated by quantitative reverse-transcription polymerase chain reaction. The levels of tumor necrosis factor-alpha (TNFalpha), which stimulates these chemokine productions, were also monitored after liver transplantation. RESULTS The accumulated PMN number, and lung edema, quantified by wet to dry weight ratio, significantly increased in the 24-hr cold-ischemia group after 3h of reperfusion, compared with the 1-hr and 6-hr cold-ischemia groups. Both pulmonary MIP-2 and CINC mRNA expression in the 24-hr group were remarkably upregulated at this time. According to the histological examination, pulmonary injury in the 24-hr group was prominent, characterized by interstitial edema, and alveolar hemorrhage. Furthermore, TNF in the hepatic vein was detected only in the 24-hr group. CONCLUSIONS Cold ischemia time prolongation upregulates pulmonary MIP-2 and CINC expression via hepatic-derived TNFalpha, and promotes PMN accumulation, resulting in increased pulmonary injury after liver transplantation.