Rabbit sera injected intraperitoneally into BALB/c mice were noted to produce a considerable and selective enlargement of extrahepatic bile ducts. The gallbladder, intrahepatic ducts, liver and other organs showed no stimulaion of growth. Duct enlargement leading to widening of its outer diameter which, on average, was 3.6 times that of normal, was due entirely to an increased number of epithelial cells with prominent proliferation of intramural glandular components. There was no evidence of inflammatory bile duct injury, fibrosis or obstruction. All of the above changes were reversible and regressed slowly after discontinuation of injections. The bile duct growth-promoting factor was detected in sera of many animal species including humans and birds. Host response to this factor was determined by the number of injections and appeared to be strain-related since it was not observed in C57BL or C3H mice. The sex and age of the donor or recipient were not of any relevance to the growth response.
In order to isolate and characterize the bile duct growth factor, rabbit serum was separated into various fractions, and the effect of each fraction was tested in the animal model. Proteins in the 33 to 65% ammonium sulfate precipitate of whole rabbit sera had activity equal to that of native sera. Activity was abolished by treating this serum fraction with 1% sodium dodecyl sulfate plus proteinase K, suggesting that the bile duct growth factor is a protein. Lipids extracted from whole sera using chloroform:methanol or ultracentrifugation were devoid of activity.
These studies point to the existence of a serum protein which acts as a selective in vivo growth factor for extrahepatic bile ducts in genetically susceptible mice.
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