Short-term ethanol exposure increases the expression of kupffer cell CD14 receptor and lipopolysaccharide binding protein in rat liver

Gut-derived endotoxins (lipopolysaccharide, LPS) complexed to LPS-binding p rotein (LBP) activate liver Kupffer cells via their CD14 receptor. Pro-infl ammatory cytokines are released and this is postulated to promote liver inj ury. We previously demonstrated enhanced expression of CD14 endoroxin recep tor after 2 weeks of alcohol administration. A similar result, based on 6 w eeks of ethanol treatment, was recently reported and suggested to correlate with alcohol-induced liver injury. To establish whether this occurs prior to or after the initiation of damage, we investigated the temporal effect o f continuous ethanol exposure on the expression of CD14 and the associated LBP. In addition, we studied the effect of treatment with gadolinium chlori de (GdCl3,) that inactivates Kupffer cells and alleviates alcohol-induced l iver damage. The amount of CD14 and LBP mRNA, as determined by reverse tran scriptase-polymerase chain reaction (RT-PCR), was unchanged 4-8 h after int ragastric ethanol administration. However, after 24-48 h of repeated ethano l administration, CD14 and LBP mRNA both increased significantly and reache d a level similar to that observed after 6 weeks of ethanol exposure by liq uid diet. Immunostaining experiments with ED2 antibody demonstrated that Gd Cl3, efficiently inactivated Kupffer cells. However, there was no concomita nt reduction in the expression of CD14 mRNA, suggesting that compensatory i nfiltration by ED2-negative, but CD14-positive, macrophages had occurred. O ur results demonstrate that soon after the initiation of ethanol exposure, i.e, within 24-48 h, the hepatic expression of both the CD14 receptor and L BP is increased. This suggests that these increases could contribute to the initiation of alcoholic damage rather than being a consequence of the inju ry.