Cubero F J, Nieto N
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Rev Esp Enferm Dig. 2006 Jun;98(6):460-72. doi: 10.4321/s1130-01082006000600007.
Liver disease is a major cause of illness and death worldwide. A central component in the complex network leading to the development of alcoholic liver disease is the activation of Kupffer cells by endotoxin and other soluble mediators. Alcohol consumption induces a state of "leaky gut increasing plasma and liver endotoxin levels. When Kupffer cells become activated, they interact with a complex of proteins located on the extracellular membrane signaling to produce a wide array of soluble factors, including cytokines, chemokines, growth factors, cyclooxygenase and lipoxygenase metabolites, and reactive oxygen species such as superoxide anion, hydrogen peroxide, and nitric oxide, all of which provide physiologically diverse and pivotal paracrine effects on all other liver cell types and, ultimately, liver injury. Kupffer cells are also central to the liver homeostatic response to injury as upon cellular degenerative changes, they immediately respond to the insult and release mediators to orchestrate inflammatory and reparative responses. Thus, the homeostatic responses are initiated by Kupffer cell-derived mediators at the cellular level and underlie the liver s defense and reparative mechanisms against injury. In order to understand better the role of Kupffer cells in the onset of liver injury, animal models in which Kupffer cells are inactivated, and cell culture settings (e.g. co-cultures) are being used with promising results that advance our understanding of alcoholic liver disease.
肝脏疾病是全球范围内疾病和死亡的主要原因。导致酒精性肝病发生的复杂网络中的一个核心组成部分是内毒素和其他可溶性介质激活库普弗细胞。饮酒会导致“肠渗漏”状态，增加血浆和肝脏内毒素水平。当库普弗细胞被激活时，它们会与位于细胞外膜上的一组蛋白质相互作用，通过信号传导产生多种可溶性因子，包括细胞因子、趋化因子、生长因子、环氧化酶和脂氧化酶代谢产物，以及超氧阴离子、过氧化氢和一氧化氮等活性氧物质，所有这些物质都会对所有其他肝细胞类型产生生理上多样且关键的旁分泌作用，并最终导致肝损伤。库普弗细胞对于肝脏对损伤的稳态反应也至关重要，因为在细胞发生退行性变化时，它们会立即对损伤做出反应并释放介质来协调炎症和修复反应。因此，稳态反应是由库普弗细胞衍生的介质在细胞水平上启动的，是肝脏防御和修复损伤机制的基础。为了更好地理解库普弗细胞在肝损伤发生中的作用，正在使用使库普弗细胞失活的动物模型以及细胞培养环境（如共培养），并取得了有前景的结果，这增进了我们对酒精性肝病的理解。
