Ethanol Feeding Selectively Impairs the Spreading of Rat Perivenous Hepatocytes on Extracellular Matrix Substrates

• Published in: Alcoholism, clinical and experimental research Vol. 23; no. 10; pp. 1673 - 1680
• Main Authors: Tuma, Dean J., Smith, Teresa E., Schaffert, Courtney S., Kharbanda, Kusum K., Sorrell, Michael F.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.1999; Lippincott Williams & Wilkins
• Subjects: Alcoholic Liver Disease; Alcoholism and acute alcohol poisoning; Animals; Biological and medical sciences; Cell Adhesion - drug effects; Cell Division - drug effects; Central Nervous System Depressants - administration & dosage; Central Nervous System Depressants - pharmacology; Collagen; Ethanol - administration & dosage; Ethanol - pharmacology; Extracellular Matrix Proteins - drug effects; Extracellular Matrix Proteins - metabolism; Fibronectin; Integrins; Laminin; Liver - cytology; Liver - drug effects; Liver - metabolism; Male; Medical sciences; Rats; Rats, Wistar; Toxicology; Ethanol; Rat; Digestive system; Gene product; Toxicity; Liver; Rodentia; Oral administration; Hepatic disease; Gene expression; Long term; Fibronectin; Protein; Alcoholic beverage; Vertebrata; Mammalia; Integrin; Laminin; Hepatocyte; Animal; Collagen; Digestive diseases
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/j.1530-0277.1999.tb04060.x

Background: Hepatocytes require attachment and subsequent spreading on an extracellular matrix for their proper growth, function and survival. Our previous studies have shown that ethanol feeding selectively impairs perivenule hepatocyte attachment to various extracellular matrices. This study was undertaken to determine whether zonal differences in hepatocyte spreading in response to ethanol feeding occurs and to ascertain the influence of ethanol consumption on the zonal expression of the β1, subunit of integrins, which are the major surface receptors responsible for matrix binding and subsequent interactions. Methods: Hepatocytes from the perivenous and periportal regions of the liver were isolated by digitonin/collagenase perfusion from rats that were pair‐fed for 2 to 3 weeks with a liquid diet containing either ethanol or isocaloric carbohydrate. The ability of perivenous and periportal hepatocytes to spread on plates coated with either type IV collagen, laminin, fibronectin or polylysine was determined. In addition, the isolated cells were used for the analysis of total cellular and surface β1 integrin expression. Results: With all of the matrix substrates tested, the spreading of perivenous hepatocytes isolated from the ethanol‐fed animals was markedly impaired, while the spreading of periportal hepatocytes was essentially unaffected by ethanol feeding. Both the total cellular as well as the surface expression of the β1 integrin subunit in perivenous cells from the ethanol‐fed rats were significantly higher than from the perivenous control cells, whereas the total and surface expression of the β1 integrin in periportal cells isolated from ethanol‐fed and control rats were not significantly different. Conclusions: The results indicated that in addition to impairing hepatocyte attachment, ethanol feeding also impairs another critical step of the adhesion process, that of hepatocyte spreading on extracellular matrix substrates. This defect occurred preferentially in perivenous cells and not periportal cells and was associated with an increase in β1 integrin expression, suggesting that a compensatory mechanism occurs as an attempt by the perivenous cells to overcome impaired cell‐matrix interactions caused by ethanol. Overall, these alterations in extracellular matrix‐hepatocyte interactions could lead to alterations of hepatocyte structure and function and potentially play a role in alcoholic liver injury.