Lipopolysaccharide treatment of rats alters antigen expression and oxidative metabolism in hepatic macrophages and endothelial cells

Authors

  • Thomas W. Mc Closkey,

    1. Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08855
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  • Jeanine A. Todaro,

    1. Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08855
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  • Dr. Debra L. Laskin

    Corresponding author
    1. Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey 08855
    • Dept. of Pharmacology and Toxicology, Rutgers University, P.O. Box 789, Piscataway, NJ 08855–0789
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Abstract

Endothelial cells and macrophages are located within the hepatic sinusoids. These two cell types play an important role in the clearance of bacterially derived lipopolysaccharide from the portal circulation. Our laboratory has previously demonstrated that treatment of rats with lipopolysaccharide results in the accumulation of macrophages in the liver that display properties of activated mononuclear phagocytes. This study was designed to analyze the effects of lipopolysaccharide on hepatic endothelial cells. Female Sprague-Dawley rats were treated with 5 mg/kg of lipopolysaccharide. Macrophages and endothelial cells were isolated from the rats 48 hr later by in situ perfusion of the liver with collagenase and pronase followed by differential centrifugation and centrifugal elutriation. We found that lipopolysaccharide treatment of rats resulted in an increase in the number of both macrophages and endothelial cells recovered from the liver. Using specific monoclonal antibodies and flow cytometry, both macrophages and endothelial cells were found to express cell surface markers for Ia antigen, leukocyte common antigen, CD4 and the macrophage antigen, ED2. Macrophages expressed greater levels of these markers than endothelial cells. Flow cytometric analysis also revealed considerable subpopulation heterogeneity in the endothelial cells in antigen expression, physical characteristics and functional activity. Treatment of rats with lipopolysaccharide decreased expression of cell surface markers on the macrophages but not on the endothelial cells. This may be due to the distinct origin of these cells. To determine whether endothelial cells, like macrophages, were activated by lipopolysaccharide, we examined their ability to produce reactive oxygen intermediates. Using three different analytical methods, we found that both macrophages and endothelial cells produced reactive oxygen intermediates in response to 12-0-tetradecanoyl phorbol-13-acetate. This response was enhanced in cells from lipopolysaccharide-treated rats. Taken together, our data suggest that both endothelial cells and macrophages may be involved in the inflammatory response of the liver to lipopolysaccharide. (HEPATOLOGY 1992;16:191–203.)

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