In vivo assessment of hepatic alterations following gadolinium chloride-induced Kupffer cell blockade

Background/Aims: In recent years, Gadolinium chloride (GdCl3), a rare earth metal, has frequently been used to study the role and function of Kupffer cells under physiological and pathological conditions. This study was performed to elucidate the consequences of GdCl3-induced Kupffer cell blockade for hepatic microcirculation, hepatocellular function and integrity. Methods/Results: Using intravital fluorescence microscopy, we studied the hepatic microcirculation of rats pretreated with either GdCl3 (n=12; 10 mg/kg; 1 ml i.v. for 2 d) or saline (n=9; 1 ml). The GdCl3-treated animals revealed a significantly lower phagocytic activity of Kupffer cells when compared to controls. Concomitantly, GdCl3-treatment resulted in a pronounced rise of serum cytokine activity (tumor necrosis factor-α; interleukin-6). The hepatic microvascular perfusion was characterized by a moderate increase in the number of non-perfused sinusoids accompanied by a reduction of bile flow. In addition, GdCl3-treatment caused a slight increase in liver enzyme activity (<200 U/l) aspartate aminotransferase and alanine aminotransferase) with no substantial parenchymal tissue injury (light microscopy). The groups did not differ in concentrations of circulating endotoxin (GdCl3-treatment: 0.044±0.042 ng/ml; controls: 0.052±0.014 ng/ml). Conclusions: We conclude that hepatic alterations following Kupffer cell blockade with GdCl3 may possibly be the consequence of cytokine release as a response to the phagocytic challenge of GdCl3-aggregates. If used for Kupffer cell blockade, the hepatic alterations following GdCl3-treatment described in the present study should be taken into consideration.