Infiltration of Inflammatory Cells Expressing Mitochondrial Proteins around Bile Ducts and Intraepithelial Layer May Be Involved to the Pathogenesis in Primary Biliary Cirrhosis
Motoko Sasaki, Yuko Kakuda, Mio Kobayashi, Masami Miyakoshi, Yasunori Sato, Yasuni Nakanuma. Kanazawa University Graduate School of Medicine, Kanazawa, Japan
Background: Serum anti-mitochondrial antibodies (AMAs) are characteristics in most patients with primary biliary cirrhosis (PBC); however, the significance of AMAs in the pathogenesis of PBC has not been fully clarified, so far. We have reported the deregulated autophagy of mitochondria in biliary epithelial lesions in PBC and noticed a peculiar accumulation of mitochondrial protein-expressing inflammatory cells around bile ducts. In this study, we examined an extent, distribution and types of mitochondrial protein-expressing inflammatory cells and its association with biliary epithelial lesions in PBC.
Design: We examined the expression of pyruvate dehydrgenase complex-E2 component (PDC-E2), a major target of AMAs, and a mitochondrial protein cytochrome c oxidase, subunit I (CCO) in inflammatory cells in livers taken from patients with PBC (n=37), primary sclerosing cholangitis (PSC) (n=13), extrahepatic biliary obstruction (EBO, n=10), chronic viral hepatitis (CVH, n=25) and control normal livers (n=16). Mitochondrial protein-expressing inflammatory cells were characterized by double immunofluorescence with CD3, CD4, CD8, CD20, CD38, CD56, CD68, CD79a, CD138 or myeloperoxidase (MPO).
Results: Infiltration of mitochondrial protein-expressing inflammatory cells was mainly observed in portal tracts and around the damaged small bile ducts and in the intraepithelial layer in PBC. The extent of infiltration in portal tracts was significantly higher in PBC and early stage of CVH than normal livers (p<0.01). The extent of infiltration around bile ducts and/or intraepithelial layer was significantly higher in early stage of PBC than PSC, CVH, EBO and normal livers (p<0.01). Mitochondrial proteins-expressing inflammatory cells included the following 2 types; 1) CD68 and/or MPO-positive monocytes, macrophages or epithelioid cells and 2) CD79a, CD38 and/or CD138-positive plasmablasts and plasma cells in double fluorescence. There was no CD3-positive cells with expression of mitochondrial proteins.
Conclusions: Infiltration of mitochondrial proteins-expressing inflammatory cells was frequently observed around damaged bile ducts and intraepithelial layers in PBC. These mitochondrial proteins-expressing inflammatory cells may be closely associated in the pathogenesis of bile duct lesion in PBC.
Tuesday, March 5, 2013 1:00 PM
Poster Session IV # 152, Tuesday Afternoon