EXPRESSION OF ANTIGENS RELATED TO APOPTOSIS AND CELL-PROLIFERATION INCHRONIC NONSUPPURATIVE DESTRUCTIVE CHOLANGITIS IN PRIMARY BILIARY-CIRRHOSIS

The initial injury in primary biliary cirrhosis (PBC) is the destructi on of portal bile ducts. Little information is available on apoptosis and cell proliferation in such bile ducts, so we used immunohistochemi cal techniques to locate molecules related to apoptosis [Fas antigen, Lewis Y antigen (BM1/JIMRO), and bcl-2 protein] and to cell proliferat ion (proliferating cell nuclear antigen, PCNA) in 21 patients with PBC . In addition, nick-end labelling was done to locate DNA fragmentation . The expression of these molecules in chronic nonsuppurative destruct ive cholangitis (CNSDC) was examined. Cell death and PCNA expression w ere both found in portal bile ducts affected by CNSDC in 7 of the 13 C NSDC patients examined. Fas antigen was found on the plasma membrane a nd rough endoplasmic reticulum of bile-duct cells with CNSDC in the fr ozen sections of all 6 patients with CNSDC out of the 9 patients inspe cted, and this antigen was found also in bile-duct cells without CNSDC in 2 of these 9 patients. It was not found in anatomically normal liv er (from 2 patients with Gilbert's disease). The Lewis Y antigen was f ound in bile ducts with CNSDC and in proliferated ductules in all 16 p atients examined. No bcl-2 protein was found in any bile-duct or ductu le cells, but it was found in the cytoplasm of lymphocytes surrounding or invading CNSDC. DNA fragmentation was found in the nuclei of bile- duct cells with CNSDC by nick-end labelling. Our study indicated that Fas-mediated apoptosis might be involved in CNSDC, but that bcl-2 prot ein seems to participate less than Fas. Although the Lewis Y antigen w as found in many bile ducts, the relationship between the antigen and apoptosis remains unknown because there was no evidence that this anti gen mediates apoptosis.