Strey Christoph W, Markiewski Maciej, Mastellos Dimitrios, Tudoran Ruxandra, Spruce Lynn A, Greenbaum Linda E, Lambris John D
Protein Chemistry Laboratory, Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Exp Med. 2003 Sep 15;198(6):913-23. doi: 10.1084/jem.20030374.
Complement has been implicated in liver repair after toxic injury. Here, we demonstrate that complement components are essential for liver regeneration, and mediate their effect by interacting with key signaling networks that promote hepatocyte proliferation. C3- or C5-deficient mice exhibited high mortality, parenchymal damage, and impaired liver regeneration after partial hepatectomy. Mice with dual C3 and C5 deficiency had a more exacerbated phenotype that was reversed by combined C3a and C5a reconstitution. Interception of C5a receptor signaling resulted in suppression of IL-6/TNFalpha induction and lack of C3 and C5a receptor stimulation attenuated nuclear factor-kappaB/STAT-3 activation after hepatectomy. These data indicate that C3a and C5a, two potent inflammatory mediators of the innate immune response, contribute essentially to the early priming stages of hepatocyte regeneration.
补体已被证明与毒性损伤后的肝脏修复有关。在此，我们证明补体成分对肝脏再生至关重要，并通过与促进肝细胞增殖的关键信号网络相互作用来介导其作用。C3或C5缺陷型小鼠在部分肝切除术后表现出高死亡率、实质损伤和肝脏再生受损。C3和C5双缺陷型小鼠的表型更为严重，联合补充C3a和C5a可使其逆转。阻断C5a受体信号导致IL-6/TNFα诱导受到抑制，缺乏C3和C5a受体刺激会减弱肝切除术后核因子-κB/STAT-3的激活。这些数据表明，C3a和C5a这两种先天免疫反应的强效炎症介质，对肝细胞再生的早期启动阶段起着至关重要的作用。
