Tumor necrosis factor-alpha cell-surface receptors of liver parenchymal and nonparenchymal cells during acute and chronic alcohol administration to rats

Alcohol Clin Exp Res. 1995 Apr;19(2):332-8. doi: 10.1111/j.1530-0277.1995.tb01511.x.


Tumor necrosis factor-alpha (TNF-alpha) has been shown to contribute to the alcohol [ethanol (ETOH)]-induced alteration of hepatic function. Therefore we tested the hypothesis that the hepatic action of TNF-alpha could be due, at least in part, to alterations in TNF-alpha cell-surface receptors of hepatic parenchymal (hepatocytes) and nonparenchymal (Kupffer and sinusoidal endothelial) cells. Rats were either acutely treated with ETOH by a primed, continuous 7-hr intravenous infusion of 20% (w/v) ETOH (30 mg/100 g body weight/h) or chronically fed an ETOH-containing liquid diet (5.2% ETOH, w/v, with ETOH as 36% of total calories) for 14 weeks. Control rats in the acute group were infused with sterile saline, whereas control rats in the chronic group were fed liquid diet containing dextrin to replace ETOH in isocaloric amounts. Three hr before killing, the rats were injected intravenously with Gram-negative bacterial lipopolysaccharide [(LPS) 100 micrograms/100 g body weight] or saline. Hepatocytes, Kupffer cells, and sinusoidal endothelial cells were isolated after liver perfusion with collagenase (without pronase), separated by centrifugal elutriation, and used to determine the affinity (Kd) and capacity (Bmax) of binding sites, using recombinant human-[125I]TNF-alpha as the ligand. Two binding sites were detected on Kupffer cells and sinusoidal endothelial cells isolated from control animals: a high-affinity (Kd1, in the range of 150-200 pM), low-capacity (Bmax, in the range of 2-3 fmol/10(6) cells) binding site and a low-affinity (Kd2, in the range of 2-9 nM), high-capacity (Bmax2, in the range of 3-15 fmol/10(6) cells) binding site.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alcoholic Intoxication / pathology*
  • Alcoholism / pathology*
  • Animals
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / pathology
  • Kupffer Cells / drug effects
  • Kupffer Cells / pathology
  • Lipopolysaccharides / pharmacology
  • Liver / drug effects*
  • Liver / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Tumor Necrosis Factor / drug effects*
  • Receptors, Tumor Necrosis Factor / physiology
  • Tumor Necrosis Factor-alpha / physiology*


  • Lipopolysaccharides
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha