Effect of acute and chronic alcohol administration to rats on the expression of interleukin-6 cell-surface receptors of hepatic parenchymal and nonparenchymal cells.
Rats were treated with alcohol either acutely (continuous, 7-hr intravenous infusion; blood alcohol levels approximately 35 mM) or chronically (liquid diet, 12-14 weeks). Three hr before killing, the animals received Gram-negative bacterial lipopolysaccharide (LPS) or saline. Hepatocytes, Kupffer cells, and liver sinusoidal endothelial cells were isolated by liver collagenase perfusion and centrifugal elutriation, and used for measurements of recombinant human [125I]interleukin-6 binding. Dissociation constant (Kd) and the amount of cell-surface receptors (Bmax) were measured on whole cells, at 4 degrees C. Two binding sites were detected on all three cell types: high-affinity (Kd1, from 20 to 125 pM) and low-affinity (Kd2, from 0.2 to 2 nM), with low Bmax (Bmax, from 0.4 to 12 fmol/10(6) cells) and high Bmax (Bmax2, from 10 to 210 fmol/10(6) cells). Hepatocytes displayed an 8-fold higher binding capacity for high-affinity sites (Bmax1) than the other two cell types. Acute ethanol treatment induced the following significant changes in the binding parameters: a decrease in Kd1 for hepatocytes and Kupffer cells, an increase in Bmax2 for hepatocytes, and a decrease in Bmax1 for Kupffer cells. Although the control (nonalcoholic) liquid diet per se completely suppressed the high-affinity binding sites, alcohol-containing diet induced only one change: a significant increase in Kd2 for hepatocytes. No changes in the binding parameters were seen after LPS administration to the chronically treated group. In the acute group, LPS mimicked alcohol action on hepatocyte binding parameters. Alcohol blunted LPS effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112-1393.
I V
IV
Deaciuc
J M
JM
Alappat
N B
NB
D'Souza
D000210:Acute-Phase Reaction / Q000235:genetics / Q000473:pathology; D000437:Alcoholism / Q000235:genetics* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D007728:Kupffer Cells / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000235:genetics*; D019947:Receptors, Interleukin-6
D008070:Lipopolysaccharides; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6