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首页> 外文期刊>American Journal of Physiology >Complement Factor D protects mice from ethanol-induced inflammation and liver injury
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Complement Factor D protects mice from ethanol-induced inflammation and liver injury

机译：补体因子D保护小鼠免受乙醇诱导的炎症和肝损伤

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Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While complement component 1, Q subcomponent (Clq)-dependent complement activation contributes to ethanol-induced liver injury, the role of the alternative pathway in ethanol-induced injury is unknown. Activation of complement via the classical and alternative pathways was detected in alcoholic hepatitis patients. Female C57BL/6J [wild type (WT)], Clq-deficient (Clqa-/-, lacking classical pathway activation), complement protein 4-deficient (C4-/- , lacking classical and lectin pathway activation), complement factor D-deficient (FD-/-, lacking alternative pathway activation), and Clqa/FD-/- (lacking classical and alternative pathway activation) mice were fed an etha-nol-containing liquid diet or pair-fed control diet for 4 or 25 days. Following chronic ethanol exposure, liver injury, steatosis, and pro-inflammatory cytokine expression were increased in WT but not Clqa-/- , C4-/-, or Clqa/FD-/- mice. In contrast, liver injury, steatosis, and proinflammatory mediators were robustly increased in ethanol-fed FD-/- mice compared with WT mice. Complement activation, assessed by hepatic accumulation of Clq and complement protein 3 (C3) cleavage products (C3b/iC3b/C3c), was evident in livers of WT mice in response to both short-term and chronic ethanol. While Clq accumulated in ethanol-fed FD-/- mice (short term and chronic), C3 cleavage products were detected after short-term but not chronic ethanol. Consistent with impaired complement activation, chronic ethanol induced the accumulation of apoptotic cells and fibrogenic responses in the liver of FD-/- mice. These data highlight the protective role of complement factor D (FD) and suggest that FD-dependent amplification of complement is an adaptive response that promotes hepatic healing and recovery in response to chronic ethanol.
机译：补充在凋亡细胞的微生物防御和间隙中起着至关重要的作用。新兴的证据表明补充是含酒精肝病的重要贡献者。虽然补体组分1，Q子组分（CLQ） - 依赖性补充激活有助于乙醇诱导的肝损伤，但替代途径在乙醇诱导的损伤中的作用是未知的。在酒精肝炎患者中检测到通过经典和替代途径的补体激活。雌性C57BL / 6J [野生型（WT）]，CLQ缺陷（CLQA - / - 缺乏经典途径激活），补体蛋白4缺陷（C4 - / - 缺乏经典和凝集素途径激活），补充因子D-缺乏（FD - / - 缺乏替代途径激活）和CLQA / FD - / - （缺乏经典和替代途径激活）小鼠喂养含Etha-NOL的液体饮食或对喂养的控制饮食4或25天。在慢性乙醇暴露之后，WT但不是Clqa - / - / - 或Clqa / FD - / - 小鼠的肝损伤，脂肪变性和促炎细胞因子表达增加。相反，肝损伤，脂肪变性和促炎介质在与WT小鼠相比的乙醇喂食FD - / - 小鼠中鲁棒地增加。通过CLQ和补体蛋白3（C3）切割产物（C3B / IC3B / C3C）的肝脏积累评估的补体激活，在WT小鼠的肝脏中，响应短期和慢性乙醇是明显的。而CLQ累积在乙醇喂养的FD - / - 小鼠（短期和慢性）中，短期但不慢性乙醇后检测C3切割产物。与补体激活损害，慢性乙醇诱导凋亡细胞积累和FD / - 小鼠肝脏中的纤维抗应答。这些数据突出了补体因子D（FD）的保护作用，并表明补品的FD依赖性扩增是促进肝愈合和回收响应慢性乙醇的适应性反应。

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