Acute Liver Necrosis In Nude Mice Caused By Xenografting Of Normal Human Colon Mucosa

Blood transmissible acute liver necrosis (ALF) was found in nude mice xenografted with normal human colon mucosa when we investigated mechanism of colon mucosal lymphocyte migration associated liver metastasis from colon carcinoma. The animals were prevented from liver damage when they received mononuclear cell isolated from peripheral blood of BALb/c mouse. The protection was much more stronger when the BALb/c mouse was injected with the serum from the animals of liver necrosis. To investigate the pathogenesis and mechanism, initial results were shown as following.(1)ALF was found only in nude mice of both xenografted with the mucosa and serum delivered. The incidence of mucosa xenografted mice was 91.67%(22/24) and mortality of 100%( 18/18). The serum transmitted mice were suffered from the same disease at 100% in both incidence and mortality .(2)The liver pathological examination show the portal track infiltrate of mononuclear cells, piece meal necrosis and inter-lobule massive necrosis, apoptosic bodies, fibrosis regeneration of liver cells.(3)Blood tests for liver functions, such as serum alanine transamines (ALT), total protein (TP), total bilirubin (BILIT) and blood urea nitrogen (BUN) show positive change.(4)No viral particles neither bacteria were found under electronic scope.(5)Immunological data. Serum LPS, TNF, IL-1, IL-2, IL-6 increased in both nude and BALb/c mice xenografted with the mucosa and the suspension control. Immuno-histochemistry show increase of CD8+ T cells in peripheral blood as well as in the liver tissue of the ill animals.(6)blood anti-mouse-hepatitis-virus (MHV) antibodies were positive only in the BALb/c mice who received the serum.(7)Protective efficacy was found when peripheral blood mononuclear cells(PMNC) infused into the nude mice at the same time of the nosogenetic serum injection. The protection was much more stronger when the PMNCs were isolated. From the BALb/c mice attacked by the serum previously. The animals show mild inflammation without massive necrosis in the liver andsurvived longer than 30 days, which was a dose-dependent regulation.(D Plasma protein electrophoresis by SDS-PAGE displayed an abnormal band about 40kd (P40), which has a novel sequence in the first 15 animo-acid from N-terminal Blood concentration of P40 increased in nude mice and reduced in BALb/c mice by the time going on after administration of the pathogenic plasma. Purified P40 did not induced ALF, but the plasma deleted P40 show weaker pathogenicity than the whole one.Conclusions. The pathological changing of our model were better matched with that in human beings than other animal models previousely. The results show that the model was useful to find unknown pathogenic factors from the gut. Based on the model, the main pathogenic might be some viruses and unknown active factors from the mucosa rather than pure viruses or LPS. The results implied some unknown pathogenic factors in the plasma (including P40), which were related with liver necrosis.