Depressed liver regeneration after partial hepatectomy of germ-free, athymic and lipopolysaccharide-resistant mice

Authors

  • Robert P. Cornell Ph.D,

    Corresponding author
    1. Division of Science, Northeast Missouri State University Department of Microbiology, Kirksville, Mo 63501
    • Division of Science, Northeast Missouri State University, Kirksville, Mo 63501
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  • Barbara L. Liljequist,

    1. Division of Science, Northeast Missouri State University Department of Microbiology, Kirksville, Mo 63501
    Current affiliation:
    1. Department of Surgery, University of Wisconsin School of Medicine, Madison, WI 53706
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  • Kenneth F. Bartizal

    1. Departments of Immunology, Kirksville College of Osteopathic Medicine, Kirksville, Mo 63501
    Current affiliation:
    1. Merck and Company, Inc., Department of Basic Microbolog, P.O. Box 2000 (R80 T100), Rahway, NJ 07065–0900
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Abstract

A hypothesis has been proposed by this laboratory that endogenous gut-derived lipopolysaccharide is responsible for systemic endotoxemia in animals with acute liver injury particularly after partial (67%) hepatectomy. Systemic lipopolysaccharide and possibly fibrin aggregates or tissue debris then elicit release of cytokines from phagocytizing macrophages and/or monocytes that may be essential for normal liver regeneration. To test this hypothesis liver regeneration was assessed in germ-free euthymic mice that lack the gram-negative bacterial source of lipopolysaccharide, as well as being deficient in lymphoid tissue and relatively resistant to endotoxin. To complement the germ-free animals, conventional athymic nude BALB/c mice and conventional lipopolysaccharide-resistant C3H/HeJ mice were also examined. Liver regeneration, quantified by [3H] thymidine incorporation into hepatic DNA after partial hepatectomy was performed on mice anesthetized with ether, was significantly depressed in germ-free euthymic and conventional athymic BALB/c mice and delayed in conventional lipopolysaccharide-resistant C3H/HeJ mice, as compared with conventional control BALB/c and C3H/HeN animals. Pretreatment of conventional euthymic control mice with lipopolysaccharide 24 hr before surgery significantly stimulated hepatic DNA synthesis after 67% liver resection. Germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice pretreated with endotoxin did not manifest significant stimulation of liver regeneration. Evidence is reviewed that cytokine release in response to endotoxin was depressed in germ-free euthymic, conventional athymic, and conventional lipopolysaccharide-resistant mice as compared with conventional euthymic controls. The inability to release cytokines in response to gut-derived endotoxin in the three murine strains studied or the paucity of endogenous lipopolysaccharide in germ-free animals may explain the significant depression or delay of liver regeneration as compared with conventional euthymic control mice.(HEPATOLOGY 1990;11:916-922.).

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