Storage solution containing fructose-1,6-bisphosphate inhibits the excess activation of Kupffer cells in cold liver preservation.

Abstract

In liver transplantation, the activation of Kupffer cells at the time of cold preservation and reperfusion is considered to play an important role. In the present study, the usefulness of cold storage solution containing fructose-1,6-bisphosphate (FBP) was compared with University of Wisconsin (UW) solution in the function of Kupffer cells. Kupffer cells were separated from rat liver stored at 4 degrees C in each storage solution. Four kinds of storage solutions were used: UW, simplified UW without FBP (0-FBP), and solutions with 10 or 20 mM FBP (10-FBP, 20-FBP). Lipopolysaccharide (LPS) labeled by fluorescein was loaded after 12 or 24 hr of cold preservation in each solution. The rates of cells uptaking LPS as phagocytic ability were measured using flow cytometry. Tumor necrosis factor-alpha, cytokine-induced neutrophil chemoattractant, and nitric oxide (NO) were measured in the supernatant. Tumor necrosis factor-alpha values in the 20-FBP group were significantly lower than those in the UW group. Cytokine-induced neutrophil chemoattractant values at 60 min after loading LPS were significantly lower in the 20-FBP group than in the UW group. NO values at 24 hr after loading LPS were significantly lower in the 20-FBP group compared with the UW group. The 20-FBP group was highest in the rates of cells uptaking LPS after 24-hr cold preservation. The storage solution containing FBP controlled the secretion of cytokines and NO from Kupffer cells and maintained phagocytic ability. This solution was considered to be more useful than UW solution for Kupffer cell protection.