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Differential Effects of GdCl 3 ‐ or MDP Treatment on Rat Liver Microcirculation and Gene Expression in the Hepatic Non‐Parenchymal Cell Fraction in LPS Shock
Author(s) -
Henrich Dirk,
Lehnert Mark,
Herzog Carsten,
Niederlaender Stephan,
Relja Borna,
Conzelmann Lars,
Marzi Ingo
Publication year - 2008
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1080/10739680701675213
Subject(s) - microcirculation , lipopolysaccharide , shock (circulatory) , parenchyma , intravital microscopy , gene expression , endocrinology , medicine , chemistry , biology , pathology , gene , biochemistry
Background: Dichloromethylenebisphosphonate (MDP) and gadolinium chloride (GdCl 3 ) 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 GdCl 3 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 GdCl 3 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: GdCl 3 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 GdCl 3 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 GdCl 3 application prior to LPS shock. Conclusions: The results show that GdCl 3 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.