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Multiple systems organ failure. Modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells
Abstract:
The etiology of hepatic insufficiency associated with the multiple systems organ failure (MSOF) syndrome is unclear. The authors have investigated the possibility that a macrophage/Kupffer cell mediated modulation of hepatocyte function may play a role in this phenomenon. Isolated rat hepatocytes were cultured, and their rate of protein synthesis was measured by cpm of 3H leucine incorporation into protein. Nonparenchymal rat liver cells (NPC) comprised of 35-40% Kupffer cells were added to hepatocytes to establish a co-culture with or without endotoxin. Neither NPC alone nor endotoxin alone affected hepatocyte protein synthesis. However, in the presence of endotoxin, NPC caused a marked diminution of hepatocyte protein synthesis (4,396 +/- 449 cpm) compared with control hepatocytes (10,943 +/- 623 cpm). No change in microscopic morphology or ability to exclude trypan blue occurred. This modulation of hepatocyte function by an endotoxin stimulated Kupffer cell preparation may, in part, represent the mechanism of hepatic insufficiency associated with the MSOF syndrome.
Insights
Kupffer cells, stimulated by endotoxin, significantly reduce liver cell protein synthesis. This finding suggests a potential mechanism for hepatic insufficiency in multiple systems organ failure (MSOF).
Area of Science:
- Hepatology
- Immunology
- Cell Biology
Background:
- The causes of liver dysfunction in multiple systems organ failure (MSOF) are not fully understood.
- Investigating the role of immune cells in liver injury is crucial for understanding MSOF.
Purpose of the Study:
- To explore if Kupffer cells mediate liver cell dysfunction in MSOF.
- To investigate the impact of endotoxin-stimulated Kupffer cells on hepatocyte function.
Main Methods:
- Co-culture of isolated rat hepatocytes with nonparenchymal liver cells (NPCs) rich in Kupffer cells.
- Measurement of hepatocyte protein synthesis using 3H leucine incorporation.
- Inclusion of endotoxin to stimulate Kupffer cells.
Main Results:
- Endotoxin-stimulated Kupffer cells markedly reduced hepatocyte protein synthesis.
- Hepatocyte protein synthesis decreased from 10,943 +/- 623 cpm to 4,396 +/- 449 cpm in co-cultures with endotoxin.
- No changes in hepatocyte morphology or viability were observed.
Conclusions:
- Endotoxin-activated Kupffer cells can significantly impair hepatocyte protein synthesis.
- This Kupffer cell-mediated modulation may contribute to hepatic insufficiency in MSOF syndrome.