The role of complement activation in tumour necrosis factor-induced lethal hepatitis.
The role of complement activation in tumour necrosis factor-induced lethal hepatitis.
复制标题
补体激活在肿瘤坏死因子诱导的致死性肝炎中的作用。
DOI：
10.1006/cyto.1998.0462
复制
发表时间：
1999
期刊：
影响因子：
3.8
通讯作者：
Brouckaert,P
中科院分区：
文献类型：
--
作者：
Libert,C;Wielockx,B;Grijalba,B;VanMolle,W;Kremmer,E;Colten,HR;Fiers,W;Brouckaert,P
在动物体内注射肿瘤坏死因子 (TNF) 会导致严重的肝细胞毒性，尤其是同时注射 D-(+)-半乳糖胺 (GalN) 时。用 TNF/GalN 攻击后，血清补体活性（CH50 和 APCH50）急剧下降，表明经典途径和替代途径均被强烈激活。单独使用 TNF 或 GalN 则没有这样的效果。补体蛋白 C3 [C3(b)] 的裂解产物沉积在 TNF/GalN 处理小鼠的肝细胞表面。静脉注射眼镜蛇毒因子（CVF）会消耗补体，从而抑制肝炎的发展。然而，CVF 预处理也可以保护 C3 缺陷小鼠。尽管抗 C1q 抗体已耗尽血浆 C1q，但用 C1q 耗尽抗体预处理小鼠并不能防止 TNF/GalN 致死。通过基因靶向产生的 B 因子缺陷和 C3 缺陷小鼠被证明与对照小鼠一样对 TNF/GalN 敏感。此外，在 C3 缺陷小鼠中，血小板活化因子（TNF 诱导的肝衰竭的重要介质）诱导的致死性休克并未减少。这些数据表明，补体虽然被激活，但在该模型中急性致死性肝衰竭的发生中并不起主要作用，并且 CVF 诱导的保护与补体耗竭无关。
Injection of tumour necrosis factor (TNF) in animals causes severe liver cell toxicity, especially when D-(+)-galactosamine (GalN) is co-administered. After challenge with TNF/GalN, serum complement activity (CH50 and APCH50) decreased dramatically, suggesting strong activation of both the classical and the alternative pathways. TNF or GalN alone had no such effect. A cleavage product of complement protein C3 [C3(b)] was deposited on the surface of hepatocytes of TNF/GalN-treated mice. Intravenous administration of cobra venom factor (CVF), which depletes complement, inhibited the development of hepatitis. However, CVF pretreatment also protected C3-deficient mice. Pretreatment of mice with a C1q-depleting antibody did not prevent TNF/GalN lethality, although the anti-C1q antibody had depleted plasma C1q. Factor B-deficient and C3-deficient mice, generated by gene targeting, proved to be as sensitive to TNF/GalN as control mice. Furthermore, induction of lethal shock by platelet-activating factor, an important mediator in TNF-induced hepatic failure, was not reduced in C3-deficient mice. These data indicate that complement, although activated, plays no major role in the generation of acute lethal hepatic failure in this model and that CVF-induced protection is independent of complement depletion.