D. Ruttinger et al., IN-VIVO ASSESSMENT OF HEPATIC ALTERATIONS FOLLOWING GADOLINIUM CHLORIDE-INDUCED KUPFFER CELL BLOCKADE, Journal of hepatology, 25(6), 1996, pp. 960-967
Background/Aims: In recent years, Gadolinium chloride (GdCl3), a rare
earth metal, has frequently been used to study the role and function o
f Kupffer cells under physiological and pathological conditions. This
study was performed to elucidate the consequences of GdCl3-induced Kup
ffer cell blockade for hepatic microcirculation, hepatocellular functi
on and integrity. Methods/Results: Using intravital fluorescence micro
scopy, 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 phagoc
ytic activity of Kupffer cells when compared to controls. Concomitantl
y, GdCl3-treatment resulted in a pronounced rise of serum cytokine act
ivity (tumor necrosis factor-alpha; interleukin-6). The hepatic microv
ascular perfusion was characterized by a moderate increase in the numb
er 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 aminotrans
ferase) with no substantial parenchymal tissue injury (light microscop
y). The groups did not differ in concentrations of circulating endotox
in (GdCl3-treatment: 0.044 +/- 0.042 ng/ml; controls: 0.052 +/- 0.014
ng/ml). Conclusions: We conclude that hepatic alterations following Ku
pffer cell blockade with GdCl3 may possibly be the consequence of cyto
kine release as a response to the phagocytic challenge of GdCl3-aggreg
ates. If used for Kupffer cell blockade, the hepatic alterations follo
wing GdCl3-treatment described in the present study should be taken in
to consideration.