Expression of antigens related to apoptosis and cell proliferation in chronic nonsuppurative destructive cholangitis in primary biliary cirrhosis

Abstract

The initial injury in primary biliary cirrhosis (PBC) is the destruction of portal bile ducts. Little information is available on apoptosis and cell proliferation in such bile ducts, so we used immunohistochemical techniques to locate molecules related to apoptosis [Fas antigen, Lewis Y antigen (BM1/JIMRO), and bcl-2 protein] and to cell proliferation (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 destructive cholangitis (CNSDC) was examined. Cell death and PCNA expression were both found in portal bile ducts affected by CNSDC in 7 of the 13 CNSDC patients examined. Fas antigen was found on the plasma membrane and rough endoplasmic reticulum of bile-duct cells with CNSDC in the frozen sections of all 6 patients with CNSDC out of the 9 patients inspected, 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 liver (from 2 patients with Gilbert's disease). The Lewis Y antigen was found in bile ducts with CNSDC and in proliferated ductules in all 16 patients examined. No bcl-2 protein was found in any bile-duct or ductule 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 protein seems to participate less than Fas. Although the Lewis Y antigen was found in many bile ducts, the relationship between the antigen and apoptosis remains unknown because there was no evidence that this antigen mediates apoptosis.

Immortalized intrahepatic mouse biliary epithelial cells: Immunologic characterization and immunogenicity

“…It is intriguing to speculate that such heterogeneity may involve differential expression of FAS/APO-1 (CD95), the ''death receptor'' for apoptosis that is activated by FAS-ligand on CTL. 16 BEC expression of FAS/APO-1 has been identified in biopsies of patients with PBC 13,15 and normal human fetal liver. 51 In the latter, only some of the BEC expressed FAS/APO-1 in a given tissue section.…”

“…11 BEC in PBC also expressed costimulatory B7-1 (CD80), B7-2 (CD86), 14 and the apoptosis receptor, FAS/APO-1. 15 Collectively, these phenotypic changes indicate that BEC may be targets for either class I MHC-restricted CD8 or class II MHC-restricted CD4 CTL bearing FAS-ligand 16 and might function as ''professional'' antigen-presenting cells (APC). 17 However, the capacity to study the immunopathogenesis of NSDC and the immunologic function of isolated [18][19][20][21] or immortalized [22][23][24] human BEC remains limited.…”

Interleukin-17A-Induced Epithelial-Mesenchymal Transition of Human Intrahepatic Biliary Epithelial Cells: Implications for Primary Biliary Cirrhosis

“…Ultimately, any model for PBC pathogenesis must be able to explain IBECs loss and the development of progressive ductopenia. Initial researches suggested that apoptosis was an important mechanism for IBECs loss in livers of PBC (Kuroki et al 1996;Harada et al 1997;Tinmouth et al 2002;Kawata et al 2012). Nevertheless, the apoptosis of IBECs is thought to be predominant in the middle groups male female Age (years) IL-17A (pg/ml) PBC 2 27 51.5 ± 14.2 2.63 ± 1.27 * Health control 2 9 46.9 ± 12.5 1.89 ± 0.52…”

Ebselen Protects against the Reduction in Levels of Drug‐Metabolizing Enzymes in Livers of Rats with Deoxycholic Acid‐Induced Liver Injury

“…Hydrophobic bile acids induce apoptosis in rat hepatocytes (Patel et al 1994). It is known that apoptotic changes occur in hepatocytes during primary biliary cirrhosis (Kuroki et al 1996).…”