Mediators Released from the Kupffer Cell

(1)库普弗细胞与肝细胞或其他窦状细胞的相互作用。我们在体外研究中发现，产生前列腺素的库普弗细胞保护受损的肝细胞，细胞降解肝细胞产生的胶原，激活的库普弗细胞释放IL-6作用于肝细胞产生CRP，此外，内毒素激活的库普弗细胞释放TNF，但其数量远少于脾脏活化的巨噬细胞。同时发现坑细胞的活化和增殖伴随着Kupffer细胞的活化。在长期乙醇喂养的大鼠中，Kupffer细胞的内吞活性明显降低。从长期乙醇喂养的大鼠中分离和培养的Kupffer细胞也显示出内吞功能下降。窦状内皮细胞似乎是对库普弗细胞功能障碍的代偿。(2) Kupffer细胞在肝损伤发病机制中的作用。在酒精性肝炎实验模型中，内毒素诱导的TNF在肝损伤的发病机制中发挥重要作用。然而，脾切除术明显抑制肝损伤，提示巨噬细胞在脾脏中起重要作用。在半乳糖胺诱导的肝损伤中也得到了类似的结果。这些数据表明，肝脏巨噬细胞Kupffer细胞的功能与脾脏巨噬细胞不同，Kupffer细胞对肝脏的保护作用更强，脾脏巨噬细胞在肝损伤的发病机制中更重要。

(1) Interaction between the Kupffer cell and hepatocytes or other sinusoidal cells. It has been found in our in vitro studies that the Kupffer cell producing Prostaglandin protects injured hepatocytes, the cell degradates collagens produced by hepatocytes, activated Kupffer cells releasing IL-6 acts to the hepatocyte for the production of CRP, in addition, endotoxin activated Kupffer cells release TNF, however, its amount is much less than that by activated macrophages in the spleen. It was also found that the activation and priloferation of pit cells accompanies with activated Kupffer cells. In chronic ethanol-fed rats, the Kupffer cell showed to have a remarkably depressed endocytotic activity. Isolated and cultured Kupffer cells taken from chronically ethanol-fed rats revealed to be also in depressed endocytotic function. The sinusoidal endothelial cell appeared to be compensatory for the Kupffer cell dysfunction.(2) Role of the Kupffer cell in pathogenesis of liver injures. In the experimental model of alcoholic hepatitis, endotoxin-induced TNF showed to play an important role in pathogenesis of liver injury. However, splenectomy inhibits liver injuries remarkably, suggesting of an important role of macrophages in the spleen. Similar results were also obtained in Galactosamine-induced liver injury. These data show that functions of Kupffer cells, macrophages in the liver, are different from those of macrophages in the spleen and the Kupffer cell appears to be more protective for the liver and the macrophage in the spleen appears to be more important in pathogenesis of liver injuries.