Impaired attachment of hepatocytes to extracellular matrix components after chronic ethanol administration.

BACKGROUND

Previous studies have shown that the assembly and properties of the hepatocyte plasma membrane are altered by ethanol administration, indicating possible changes in the receptor-mediated binding of the plasma membrane to extracellular matrix substrates. In the present study, the effects of chronic ethanol consumption on the ability of hepatocytes to attach to various components of the extracellular matrix were investigated.

EXPERIMENTAL DESIGN

Rats were pair-fed for 5 weeks with a liquid diet containing either ethanol (as 36% of total calories) or isocaloric carbohydrate. The effects of ethanol treatment on hepatocyte-extracellular matrix interactions was ascertained by determining the ability of isolated hepatocytes to attach to various extracellular matrix substrates.

RESULTS

The attachment of hepatocytes, isolated from the ethanol-fed rats, to laminin-coated plates was significantly decreased compared with hepatocytes from chow-fed or pair-fed controls. Greater decreases in attachment were seen when higher numbers of hepatocytes were seeded in the plates. Similar inhibitions of attachment were also observed when fibronectin or type I collagen were used as matrices. Time-course cell attachment assays indicated that the maximum extent of attachment rather than the rate of attachment was primarily altered by chronic ethanol feeding. Hepatocytes from the ethanol-fed rats also detached more readily from the matrix-coated plates than those from the controls. A reduced number of functional surface receptors for matrix components is likely the most important factor that accounts for the ethanol-induced impairment of hepatocyte attachment.

CONCLUSIONS

These results indicate that chronic ethanol administration impairs the interactions of hepatocytes with their extracellular matrix and that this defect could lead to alterations of hepatocyte structure and function.