Modulation of kupffer cell activity by gadolinium chloride in endotoxemic rats

Shock
B VollmarM D Menger

Abstract

Gadolinium chloride (GdCl3) has been reported to block Kupffer cell (KC) phagocytic activity in rats. In this study, we investigated the action of GdCl3 on Kupffer cells and related effects in response to lipopolysaccharide (LPS) exposure of rats. Using intravital fluorescence microscopy (IVFM), the hepatic microcirculation (phagocytic activity and zonal distribution of KC, sinusoidal perfusion, leukocyte-endothelial cell interaction) of rats pretreated with either saline or GdCl3 (10 mg/kg i.v. for 2 days) was studied at 1 h (n = 14) and 16 h (n = 16) after exposure to Escherichia coli LPS (10 mg/kg i.v.). LPS-exposure (1 h) resulted in KC activation with increased phagocytic activity (IVFM), intracellular enrichment of phagocytic vacuoles, and marked rise of cytokines (tumor necrosis factor-alpha, interleukin-6) in serum, whereas GdCl3-pretreatment completely inhibited the LPS-related KC response. 16 h after LPS-exposure, saline-treated animals revealed high serum levels of LPS, associated with microvascular perfusion deficits, marked KC destruction, and hepatocellular disintegration, which finally resulted in a mortality rate of 47% (7/15). In contrast, none of the GdCl3-treated animals died (0/8). GdCl3-pretreatment signifi...Continue Reading

Citations

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