West M A, Billiar T R, Mazuski J E, Curran R J, Cerra F B, Simmons R L
Department of Surgery, Washington University School of Medicine, St Louis, MO 63110.
Arch Surg. 1988 Nov;123(11):1400-5. doi: 10.1001/archsurg.1988.01400350114018.
We hypothesize that alterations of hepatocyte function in sepsis are modulated by endotoxin (lipopolysaccharide)-triggered Kupffer cells. In the present experiments the effect of lipopolysaccharide on secreted and cellular proteins synthesized by hepatocytes cultured alone or cocultured with Kupffer cells was investigated using polyacrylamide gel electrophoresis. Lipopolysaccharide had no direct effect on the types or amounts of secreted proteins synthesized by hepatocytes alone. Kupffer cells coculturing resulted in increased synthesis of some hepatocyte proteins (68k and 23k) whose production was not altered by lipopolysaccharide. In contrast, addition of lipopolysaccharide to the hepatocyte-Kupffer cell coculture substantially decreased synthesis of several proteins (73k, 66k, and 35k). Despite an overall decrease in protein synthesis of hepatocytes cocultured with Kupffer cells after the addition of lipopolysaccharide, there was increased synthesis of several individual proteins (58k and 44k). Similar effects were seen in synthesis of cellular protein. The addition of recombinant interleukin 1 to hepatocytes alone or in coculture had no effect on the amount or type of protein synthesized. We conclude that Kupffer cells regulate the types and amounts of individual proteins synthesized by hepatocytes via mediators other than interleukin 1.
我们推测，脓毒症中肝细胞功能的改变是由内毒素（脂多糖）激活的库普弗细胞所调节的。在本实验中，我们使用聚丙烯酰胺凝胶电泳研究了脂多糖对单独培养或与库普弗细胞共培养的肝细胞分泌蛋白和细胞内合成蛋白的影响。脂多糖对单独培养的肝细胞合成的分泌蛋白的类型或数量没有直接影响。与库普弗细胞共培养导致一些肝细胞蛋白（68k和23k）的合成增加，而脂多糖并未改变这些蛋白的产生。相反，在肝细胞 - 库普弗细胞共培养体系中添加脂多糖会显著降低几种蛋白（73k、66k和35k）的合成。尽管添加脂多糖后与库普弗细胞共培养的肝细胞的蛋白质合成总体上有所下降，但仍有几种个别蛋白（58k和44k）的合成增加。在细胞内蛋白合成中也观察到了类似的效应。单独或在共培养体系中向肝细胞添加重组白细胞介素1对合成蛋白的数量或类型没有影响。我们得出结论，库普弗细胞通过白细胞介素1以外的介质调节肝细胞合成的个别蛋白的类型和数量。
