Department of Microbiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
Int J Mol Sci. 2014 May 5;15(5):7711-30. doi: 10.3390/ijms15057711.
Kupffer cells reside within the liver sinusoid and serve as gatekeepers. They produce pro- and anti-inflammatory cytokines and other biologically important molecules upon the engagement of pattern recognition receptors such as Toll-like receptors. Kupffer cell-ablated mice established by in vivo treatment with clodronate liposomes have revealed many important features of Kupffer cells. In this paper, we review the importance of Kupffer cells in murine acute liver injuries and focus on the following two models: lipopolysaccharide (LPS)-induced liver injury, which is induced by priming with Propionibacterium acnes and subsequent challenge with LPS, and hypercoagulability-mediated acute liver failure such as that in concanavalin A (Con A)-induced hepatitis. Kupffer cells are required for LPS sensitization induced by P. acnes and are a major cellular source of interleukin-18, which induces acute liver injury following LPS challenge. Kupffer cells contribute to Con A-induced acute liver failure by initiating pathogenic, intrasinusoidal thrombosis in collaboration with sinusoidal endothelial cells. The mechanisms underlying these models may shed light on human liver injuries induced by various etiologies such as viral infection and/or abnormal metabolism.
枯否细胞位于肝窦内，充当守门员。它们在模式识别受体（如 Toll 样受体）被激活后，会产生促炎和抗炎细胞因子以及其他具有重要生物学意义的分子。通过体内用氯膦酸盐脂质体处理来清除枯否细胞的小鼠模型揭示了枯否细胞的许多重要特征。在本文中，我们综述了枯否细胞在小鼠急性肝损伤中的重要性，并重点关注以下两种模型：脂多糖（LPS）诱导的肝损伤，该损伤是通过痤疮丙酸杆菌的预刺激和随后的 LPS 挑战诱导的；以及高凝状态介导的急性肝衰竭，如伴刀豆球蛋白 A（Con A）诱导的肝炎。枯否细胞是痤疮丙酸杆菌诱导的 LPS 致敏所必需的，并且是白细胞介素-18 的主要细胞来源，它在 LPS 挑战后诱导急性肝损伤。枯否细胞通过与窦内皮细胞合作，引发致病的窦内血栓形成，导致 Con A 诱导的急性肝衰竭。这些模型的机制可能为各种病因（如病毒感染和/或异常代谢）引起的人类肝损伤提供启示。
