Expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver tissue.
OBJECTIVE
The objective of the present study was to analyze the expression and regulation of intercellular adhesion molecule-1 (ICAM-1) in organotypic cultures of rat liver slices, which preserve the normal microenvironment of liver cells.


METHODS
Rat liver slices were maintained in culture for 15 min to 24 h and examined for ICAM-1 expression by immunohistochemistry and Western blotting in basal conditions and after stimulation with 1000 IU/ml interferon-gamma (IFNgamma), 1000 IU/ml tumor necrosis factor-alpha (TNF alpha) and 50 microg/ml endotoxin. Immunohistochemical results were evaluated using a semiquantitative scoring system.


RESULTS
In uncultured slices, ICAM-1 was not detected on hepatocytes. In unstimulated liver slices maintained in organotypic culture, ICAM-1 was induced at the surface of scattered hepatocytes (score at 15 min, 0.33+/-0.47 and at 24 h, 1.17+/-0.69). After 4 h of stimulation, a significant increase in ICAM-1 expression by hepatocytes and adjacent sinusoidal cells, but not by intra-hepatic biliary epithelial cells, was observed for IFNgamma (score: 2.35+/-0.47) and endotoxin (score: 2.67+/-0.47), but not with TNF alpha (score: 0.66+/-0.47). After 24 h of stimulation, a further increase in the extent of ICAM-1 expression by hepatocytes was observed for IFNgamma (score: 3.67+/-0.47) and endotoxin (score: 4.0+/-0.0), and a significant overexpression of ICAM-1 by hepatocytes was detectable after treatment with TNF alpha (score: 3.67+/-0.47).


CONCLUSIONS
In rat liver organotypic cultures, TNF alpha, IFNgamma and endotoxin induce the expression of ICAM-1 in hepatocytes and adjacent sinusoidal endothelial cells, but not in portal tracts.
Oudar
O
O
Laboratoire de Biologie Cellulaire, INSERM U.327, Faculté de Médecine Xavier-Bichat, Paris, France.
Moreau
A
A
Feldmann
G
G
Scoazec
J Y
JY
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma