|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1992 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1991 : ¥1,500,000 (Direct Cost : ¥1,500,000)
To investigate immunological mechanism on the generation of alcoholic liver diseases, the role of Kupffer cell (macrophage in the liver) was checked from the point of the induction of antigenicity of acetaldehyde, and class 1 MHC on the surface of hepatocyte was checked after administration of alcohol.
Kupffer cell and hepatocyte those were isolated by collagenase perfusion and separated according to the specific gravity were incubated with acetaldehyde. Those cells were mixed with cytotoxic T lymphocyte against acetaldehyde-modified syngeneic cells (CTL). Only Kupffer cells were lysed with the reason of the existence of Class 1 MHC on its surface. This result showed the importance of class 1 MHC in immunological reaction and the lack of class 1 MHC on normal hepatocyte.
Then, ethanol administration was checked from the point of induction of class 1 MHC. Class 1 MHC was detected by cytotoxic T lymphocyte method shortly 12 hours after alcohol drinking. The level of class 1 MHC elevated ac
cording to the time up to 14 days and the comsumed volume of ethanol, but acetaldehyde epitope wasn't detected on the surface of hepatocyte from mice that were fed with ethanol. Then pair feeding with or without ethanol was done to two groups of mice isocalolically. Mice were fed up to 28 days, and hepatocytes were isolated by the method of collagenase infusion. Hepatocytes from mice fed without ethanol showed no class 1 MHC or acetaldehyde epitope on its surface. Hepatocytes from mice fed with ethanol revealed the elevated level of class 1 MHC, but no acetaldehyde adduct epitope which would be showed by CTL. Next, the cyanamide was given to mice intraperitoneally to elevate the serum level of acetaldehyde. Pair feeding was done to mice treated with or without cyanamide, and hepatocytes were checked just as same as above. Hepatocytes from mice treated with cyanamide showed only the elevated level of class 1 MHC.
So, long term feeding with ethanol and/or previous treatment with such as viral infection might be necessary to build acetaldehyde protein adduct on hepatocytes. Such speculation will be checked with same procedure in our unit. Less