Premium
Blockade of liver macrophages by gadolinium chloride reduces lethality in endotoxemic rats—analysis of mechanisms of lethality in endotoxemia
Author(s) -
Iimuro Yuji,
Yamamoto Masayuki,
Kohno Hiroshi,
Itakura Jun,
Fujii Hideki,
Matsumoto Yoshiro
Publication year - 1994
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.55.6.723
Subject(s) - lipopolysaccharide , tumor necrosis factor alpha , phagocytosis , liver injury , pharmacology , macrophage , superoxide , in vitro , lethality , shock (circulatory) , sepsis , biology , necrosis , immunology , whole blood , medicine , toxicology , biochemistry , enzyme
We investigated the effects of gadolinium chloride (GdCl 3 · 6H 2 O), which blocks phagocytosis by liver macrophages, on the mortality, blood tumor necrosis factor (TNF) levels, and hepatotoxicity in a lethal endotoxic shock rat model system [10 mg/kg body weight lipopolysaccharide (LPS) intravenously]. With administration of GdCl 3 , twice at 0.5 or 5 mg/kg, the survival rate 24 h after LPS injection was 56% and 100%, respectively, whereas the level of TNF in blood was not affected. Microscopic investigation of the liver revealed that the focal necrosis of hepatocytes under endotoxemia was completely protected by the administration of GdCl 3 at 5 mg/kg. We then investigated the effects of GdCl 3 on superoxide (O 2 ) production by isolated liver macrophages in vitro. The O 2 ‐ production by liver macrophages isolated from control rats was suppressed by GdCl 3 in a dose‐dependent manner. GdCl 3 also had a cytotoxic effect on these macrophages. The enhanced O 2 ‐ production by liver macrophages isolated from sublethal endotoxemic (1 mg/kg) rats was suppressed by pretreatment with GdCl 3 (5 mg/kg). It was suggested that lethality in endotoxemia cannot be explained only by the degree of increase in blood TNF levels and that the mechanism by which GdCl 3 reduces mortality and hepatotoxicity in endotoxemia possibly includes suppression of superoxide production by liver macrophages. J. Leukoc. Biol. 55 : 723–728; 1994.