The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury.
The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury.
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DOI：
10.1002/lt.21496
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发表时间：
2008-08
影响因子：
4.6
通讯作者：
Kupiec-Weglinski, Jerzy W.
中科院分区：
文献类型：
--
作者：
Fondevila, Constantino;Shen, Xiu-Da;Tsuchihashi, Seiichiro;Uchida, Yoichiro;Freitas, Maria Cecilia;Ke, Bibo;Busuttil, Ronald W.;Kupiec-Weglinski, Jerzy W.
补体级联反应的激活是缺血/再灌注损伤（IRI）过程中的重要事件。本研究旨在探讨膜攻击复合物（MAC; C5 b-9）在肝IRI发病机制中的作用。采集B&W/斯塔尔/rC 6（+）和C6（-）大鼠的肝脏，在4°C下储存24小时，然后将[原位肝移植（奥尔特）]移植给同系受体。有4个实验组：（1）C6（+）→C6（+），（2）C6（+）→C6（-），（3）C6（-）→C6（+），（4）C6（-）→C6（-）。在第+1天时，C6（−）OLT显示血管充血/坏死减少，与C6（+）肝脏的广泛坏死形成对比，这与受体C6状态无关（Suzuki评分：组1-4分别为7.2 ± 0.9、7.3 ± 1.3、4.5 ± 0.6和4.8 ± 0.4，P< 0.05）。C6（-）移植物受体的肝功能得到改善（血清谷草转氨酶：组1-4分别为2573 ± 488、1808 ± 302、1170 ± 111和1188 ± 184，P< 0.05）。与C6（+）移植物相比，C6（-）移植物中移植物内巨噬细胞浸润（艾德-1免疫染色）和中性粒细胞浸润（髓过氧化物酶活性）减少（P = 0.001）;这些数据通过酯酶染色（萘酚）得到证实。与C6（+）OLT相比，C6（−）OLT中促炎性干扰素-γ、白细胞介素-1 β和肿瘤坏死因子信使RNA/蛋白的表达也减少。与C6（+）OLT相比，C6（−）OLT中促凋亡caspase-3的Western印迹辅助表达减少（P = 0.006），而与C6（+）OLT相比，C6（−）OLT中抗凋亡Bcl-2/Bag-1的表达增强（P = 0.001）。与C6（−）OLT相比，C6（+）OLT中凋亡细胞的末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色增强（P < 0.05）。因此，补体系统的终末产物在肝IRI的机制中是必不可少的。这是第一个报告使用临床相关的肝脏冷缺血模型，以表明局部MAC抑制减弱IRI级联在奥尔特受体。
Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(−) rats were harvested, stored for 24 hours at 4°C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+)→C6(+), (2) C6(+)→C6(−), (3) C6(−)→C6(+), and (4) C6(−)→C6(−). At day +1, C6(−) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 ± 0.9, 7.3 ± 1.3, 4.5 ± 0.6, and 4.8 ± 0.4 for groups 1-4, respectively, P< 0.05). The liver function improved in recipients of C6(−) grafts (serum glutamic oxaloacetic transaminase: 2573 ± 488, 1808 ± 302, 1170 ± 111, and 1188 ± 184 in groups 1-4, respectively, P< 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(−) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-γ, interleukin-1β, and tumor necrosis factor messenger RNA/protein was also reduced in C6(−) OLTs in comparison with C6(+) OLTs. Western blot–assisted expression of proapoptotic caspase-3 was decreased in C6(−) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(−) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase–mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(−) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients.
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影响因子：
4.4
作者：
Nakashima, S;Qian, ZP;Baldwin, WM
通讯作者：
Baldwin, WM
DOI：
10.1152/ajprenal.2000.278.5.f747
发表时间：
2000-05-01
影响因子：
4.2
作者：
Hughes, J;Nangaku, M;Johnson, RJ
通讯作者：
Johnson, RJ
DOI：
10.1159/000234216
发表时间：
1987-01-01
期刊：
INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY
影响因子：
--
作者：
HANSCH, GM;SEITZ, M;BETZ, M
通讯作者：
BETZ, M
影响因子：
--
作者：
JAESCHKE, H;FARHOOD, A;SPITZER, JJ
通讯作者：
SPITZER, JJ
影响因子：
6.2
作者：
Lehmann, TG;Koeppel, TA;Post, S
通讯作者：
Post, S