The effect of Kupffer cell elimination on ethanol-induced liver damage in mice.
C57BL/10 mice develop inflammatory and necrotic changes in the liver, as well as raised serum ALT activities, after 9 days of exposure to ethanol vapour. If mice were injected twice with liposomes containing dichloromethylene diphosphonate (DMDP), with an interval of 5 days between the injections, there was complete elimination of Kupffer cells (hepatic macrophages) for a 9-day period starting 1 day after the first injection. The inflammatory and necrotic changes were significantly reduced in mice injected with liposomes containing DMDP as compared to uninjected mice or mice injected with empty liposomes; serum ALT activities were also significantly reduced. No significant difference was seen in serum tumour necrosis factor-alpha levels between the different groups. Kupffer cells therefore play a significant role in the development of the liver damage resulting from exposure to ethanol. Acetaldehyde production by Kupffer cells is one way in which these cells can damage hepatocytes and further work needs to be done to investigate this and other mechanisms.
D000818:Animals; D016923:Cell Death; D004002:Clodronic Acid / Q000494:pharmacology; D004337:Drug Carriers; D000431:Ethanol; D005260:Female; D007124:Immunoenzyme Techniques; D007728:Kupffer Cells / Q000187:drug effects / Q000502:physiology*; D008081:Liposomes; D008108:Liver Diseases, Alcoholic / Q000473:pathology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL
D004337:Drug Carriers; D008081:Liposomes; D004002:Clodronic Acid; D000431:Ethanol