Modulation of hepatocyte protein synthesis during co-cultivation with macrophage-rich peritoneal cells in vitro

G. A. Keller, M. A. West, J. T. Harty, F. B. Cerra and R. L. Simmons

The etiology of hepatic failure associated with the multiple-system organ failure syndrome is poorly understood. Because of indirect evidence suggesting that macrophages or Kupffer's cells may play a role in this phenomenon, macrophage-rich peritoneal cells were co-cultured with isolated rat hepatocytes. Following co-culture, the rate of hepatocyte protein synthesis, quantitated by counts per minute of tritiated leucine incorporated into protein, was significantly diminished. This modulation of hepatocyte function was not enhanced by prestimulation of macrophage-rich peritoneal cells in vivo by casein, thioglycolate, or Corynebacterium parvum. Addition of the macrophage secretory product lysozyme did not alter hepatocyte protein synthesis. This cell-mediated effect on hepatocytes could not be recreated by a macrophage-rich peritoneal cells supernatant transfer. These results support the idea that cells of macrophage lineage could mediate changes in hepatocyte function that may, in turn, play a role in the etiology of hepatic malfunction associated with the multiple-system organ failure syndrome.