Sato Keisaku, Hall Chad, Glaser Shannon, Francis Heather, Meng Fanyin, Alpini Gianfranco
Research, Central Texas Veterans Health Care System, Temple, Texas; Department of Medicine, Texas A&M Health Science Center, College of Medicine, Temple, Texas; Scott & White Digestive Disease Research Center, Scott & White, Temple, Texas.
Department of Medicine, Texas A&M Health Science Center, College of Medicine, Temple, Texas; Academic Research Integration, Department Surgery, Baylor Scott & White Healthcare, Temple, Texas.
Am J Pathol. 2016 Sep;186(9):2238-47. doi: 10.1016/j.ajpath.2016.06.003. Epub 2016 Jul 22.
Kupffer cells are the resident macrophages in the liver. They are located in hepatic sinusoid, which allows them to remove foreign materials, pathogens, and apoptotic cells efficiently. Activated Kupffer cells secrete various mediators, including cytokines and chemokines, to initiate immune responses, inflammation, or recruitment of other liver cells. Bile duct ligation (BDL) surgery in rodents is often studied as an animal model of cholestatic liver disease, characterized by obstruction of bile flow. BDL mice show altered functional activities of Kupffer cells compared with sham-operated mice, including elevated cytokine secretion and impaired bacterial clearance. Various mediators produced by other liver cells can regulate Kupffer cell activation, which suggest that Kupffer cells orchestrate with other liver cells to relay inflammatory signals and to maintain liver homeostasis during BDL-induced liver injury. Blocking or depletion of Kupffer cells, an approach for the treatment of liver diseases, has shown controversial implications. Procedures in Kupffer cell research have limitations and may produce various results in Kupffer cell research. It is important, however, to reveal underlying mechanisms of activation and functions of Kupffer cells, followed by hepatic inflammation and fibrosis. This review summarizes present Kupffer cell studies in cholestatic liver injury.
库普弗细胞是肝脏中的常驻巨噬细胞。它们位于肝血窦中，这使它们能够有效地清除异物、病原体和凋亡细胞。活化的库普弗细胞分泌各种介质，包括细胞因子和趋化因子，以启动免疫反应、炎症或招募其他肝细胞。啮齿动物的胆管结扎（BDL）手术常被用作胆汁淤积性肝病的动物模型，其特征是胆汁流动受阻。与假手术小鼠相比，BDL小鼠的库普弗细胞功能活动发生改变，包括细胞因子分泌增加和细菌清除受损。其他肝细胞产生的各种介质可调节库普弗细胞的活化，这表明在BDL诱导的肝损伤过程中，库普弗细胞与其他肝细胞协同传递炎症信号并维持肝脏稳态。阻断或清除库普弗细胞作为一种治疗肝病的方法，其意义存在争议。库普弗细胞研究中的操作存在局限性，可能在库普弗细胞研究中产生各种结果。然而，揭示库普弗细胞活化和功能的潜在机制，以及随后的肝脏炎症和纤维化，是很重要的。本综述总结了目前在胆汁淤积性肝损伤中库普弗细胞的研究。
