Analysis of mechanism of activation of kupffer cells in the liver

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The purpose of this study was to determine how GdCl3 affects Kupffer cell (KC) function and further to investigate a correlation between cytokine productions such as TNF-α or IL-6 by KC and those cytokine levels after LPS administration. Rats with or without GdCl3 were received LPS or saline vehicle. Serum samples were collected from the aorta at each time point after LPS administration for TNF-α and IL-6 measurements. Further, liver tissues were collected for pathological evaluation and immunohistochemistry. Moreover, isolated KCs were used for evaluation of phagocytosis, and production of superoxide and inflammatory cytokines. All animals died after LPS administration but GdCl3 prevented this mortality completely. TNF-α levels were increased rapidly by LPS in both groups without differences. In contrast, IL-6 levels were increased gradually and values were significantly greater in rats treated with vehicle than GdCl3. Large KCs showed greater phagocytosis than small KCs. Superoxide and TNF-α productions by isolated KCs were increased by LPS.These increases were not observed in the small KC.Further, LPS or TNF-α stimulation increased IL-6 production ; however values were significantly greater in the small KC than the large KC.ED2 positive cells were observed predominantly with some ED1 positive cells in the liver. Further EDI positive cells were increased after LPS but not ED2. Thus, functional heterogeneity was observed in the hepatic macrophage. The Large KC may be the resident hepatic macrophage and the small KC may be the peripheral monocyte/macrophage infiltrating into the liver. TNF-α derived from activated large KCs could activate small KCs. Subsequently, these small KCs are recruiting to other organs such as lung and kidney, and produce large amount of IL-6 leading to organ injuries and multiple organ failures. Thus, the liver could be the central organ in the inflammatory immune system.