Hepatic Sinusoidal Endothelial Cell in Alcoholemia and Endotoxemia

Abstract

The experimental data reviewed in this study tend to indicate that the hepatic sinusoidal endothelial cell (SEC) is, chronologically, the first hepatic cell that undergoes pathologic changes in alcoholemia. Due to its strategic position in the liver sinusoid, SEC dysfunction and structural alterations have far-reaching repercussions for the whole liver. The authors gather experimental evidence suggesting that alcohol-induced SEC alterations are mostly due to Kupffer cell activation induced by alcohol rather than to a direct action of alcohol on SEC. Once activated, the Kupffer cell secretes a spectrum of mediators that affect both function and structure of SEC. Kupffer cell activation is regarded as a result of both direct and indirect actions of alcohol on the cell. The indirect action of alcohol is ascribed to alcohol-induced elevated plasma levels of Gram-negative bacterial lipopolysaccharide (LPS), a strong activator of Kupffer cell. However, a comparison of alcohol and LPS effects on SEC functions and structure reveals that these two agents may have, under many circumstances, different actions on the SEC, at least in laboratory animals. However, this issue continues to be a matter of debate. Also the review presents justification for the necessity to extend research on mechanisms underlying alcoholic liver disease to the effects of alcohol on the SEC. Finally, several future research directions are suggested in this review to better understand the mechanisms underlying alcohol-induced liver dysfunction.