Inflammation is increasingly recognised to critically determine the clinical course and outcome of acute liver failure (ALF). On the one hand, massive hepatocyte cell death triggers immune cell activation and recruitment to the liver, which can stimulate immune-mediated liver damage. On the other hand, systemic activation of inflammation, systemic inflammatory response syndrome, promotes multiple organ failure and defective antimicrobial responses.1 Innate immune mechanisms play a prominent role in ALF. Mouse models of acute liver injury revealed that liver-resident macrophages, Kupffer cells, sense hepatocyte-mediated release of alarmins, which results in Kupffer cell activation and cytokine release.2 Hence, neutrophils and monocytes are recruited from the bloodstream to the site of injury. During the early phase after recruitment, neutrophils and monocytes have an inflammatory phenotype and aggravate tissue damage.3 4 However, there is ample experimental evidence that monocyte-derived macrophages change their phenotype in the liver, if injury has terminated, towards repair-promoting phagocytes.5 6 Up to now, the ‘human counterpart’ of inflammatory versus restorative macrophages in ALF has been vague. In this issue of Gut , Dr. Antoniades and coworkers present compelling experimental evidence from human samples and a mouse model that restorative macrophages in ALF …

中文翻译：

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修复急性肝衰竭中的巨噬细胞


人们越来越认识到炎症对于急性肝衰竭（ALF）的临床病程和结果至关重要。一方面，大量肝细胞死亡会触发免疫细胞激活并招募到肝脏，从而刺激免疫介导的肝脏损伤。另一方面，全身炎症激活、全身炎症反应综合征会促进多器官衰竭和抗菌反应缺陷。1先天免疫机制在 ALF 中发挥着重要作用。急性肝损伤小鼠模型显示，肝脏驻留巨噬细胞（库普弗细胞）感知肝细胞介导的警报素释放，从而导致库普弗细胞激活和细胞因子释放。2因此，中性粒细胞和单核细胞从血流募集到损伤部位。在招募后的早期阶段，中性粒细胞和单核细胞具有炎症表型并加剧组织损伤。3 4 然而，有充分的实验证据表明，如果损伤终止，单核细胞衍生的巨噬细胞会改变其在肝脏中的表型，转向促进修复的吞噬细胞.5 6 迄今为止，ALF 中炎症性巨噬细胞与恢复性巨噬细胞的“人类对应物”尚不清楚。在本期《肠道》杂志中，Antoniades 博士及其同事提出了来自人类样本和小鼠模型的令人信服的实验证据，证明 ALF 中的巨噬细胞可恢复……