Abstract
Background: Dichloromethylenebisphosphonate (MDP) and gadolinium chloride (GdCl3) are substances frequently used for experimental depletion of Kupffer Cells (KC) in models of endotoxin shock. The aim was to determine whether depletion of KC through pretreatment with GdCl3 or MDP alters the hepatic microcirculation during lipopolysaccharide (LPS)-induced shock in rats and to test if there are substance-specific differences. Methods: Rats received either MDP or GdCl3 or saline prior to induction of LPS shock. Hepatic microcirculation was evaluated by intravital microscopy (sinusoidal diameter, sinusoidal bloodflow, leukocyte adhesion), and the gene expression in the hepatic non-parenchymal cell fraction was determined by RT-PCR. Results: GdCl3 pretreatment prevented sinusoidal narrowing but did not restore sinusoidal blood flow and did not normalize leukocyte-endothelial interaction time after LPS. In contrast, MDP pretreatment improved hepatic microcirculation consistently for all parameters measured compared to GdCl3 pretreated animals. In the non-parenchymal cell fraction, eNOS gene expression was preserved and gene expression of TNF-α was blocked after MDP but not after GdCl3 application prior to LPS shock. Conclusions: The results show that GdCl3 and MDP cannot be used equivalently for experimental KC depletion in the condition of LPS-induced shock. These findings should be taken into consideration in studies that evaluate the role of Kupffer cells in models of endotoxin-induced shock.
This work was supported, in part, by DFG, Grant MA 1119 3-2. This work was presented in part at the 68th annual meeting of the German Society for Trauma Surgery, 19–22 October 2004, Berlin.