Contribution of CD14 to endotoxin-induced liver injury may depend on types of macrophage activation in rats.
Activated Kupffer cells and hepatic macrophages can produce massive liver necrosis through microcirculatory disturbance due to sinusoidal fibrin deposition. This mechanism is involved in the development of liver injury after endotoxin administration in rats pretreated with heat-killed Propionibacterium acnes (P.acnes) or undergoing 70% liver resection. The significance of CD14, a receptor for lipopolysaccharide and its binding protein, was evaluated in both models in relation to the activation mechanisms of Kupffer cells and hepatic macrophages. Northern blot analysis revealed that CD14 mRNA expression was increased in the liver of rats following P.acnes administration. In these rats, hepatic macrophages immediately after isolation showed marked increased of CD14 mRNA expression compared to Kupffer cells from normal rats. In contrast, CD14 mRNA expression was minimal in partially resected liver. Interleukin (IL)-18 and IL-2 mRNA expression in the liver and interferon (IFN)-gamma mRNA expression in the spleen were significantly increased in P.acnes-treated rats compared to normal rats, while these increases were absent in partially hepatectomized rats. Thus, CD14 expressed on hepatic macrophages after activation through a cytokine network of IL-18, IFN-gamma, and IL-2 may contribute to endotoxin-induced liver injury in P.acnes-treated rats. In contrast, in partially hepatectomized rats, this network may not operate during Kupffer cell activation, and the liver injury might develop through endotoxin receptors other than CD14 on the cells.
Toshima
K
K
Third Department of Internal Medicine, Saitama Medical School, Japan.
Mochida
S
S
Ishikawa
K
K
Matsui
A
A
Arai
M
M
Ogata
I
I
Fujiwara
K
K
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D006498:Hepatectomy; D007371:Interferon-gamma / Q000096:biosynthesis; D020382:Interleukin-18; D007376:Interleukin-2 / Q000096:biosynthesis; D007728:Kupffer Cells / Q000187:drug effects / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology*; D008262:Macrophage Activation / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008297:Male; D011425:Propionibacterium acnes / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000276:immunology
D016207:Cytokines; D020382:Interleukin-18; D007376:Interleukin-2; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D007371:Interferon-gamma