Distribution of pyruvate dehydrogenase dihydrolipoamide acetyltransferase (PDC-E2) and another mitochondrial marker in salivary gland and biliary epithelium from patients with primary biliary cirrhosis.
Previous studies in which quantitative immunofluorescence was used have shown that certain biliary epithelial cells in liver with primary biliary cirrhosis show increased levels of pyruvate dehydrogenase dihydrolipoamide acetyltransferase compared with controls. This study was designed to determine whether the increase in intensity of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in biliary epithelial cells is accounted for by an increase in the number of mitochondria in the same cells. A double-antibody staining technique was used with antibodies specific for pyruvate dehydrogenase dihydrolipoamide acetyltransferase and another mitochondrial inner membrane marker, recognized by the mouse monoclonal antibody MCA151A. Distribution of the antigens was studied in sections of liver and salivary gland, an additional site that is frequently involved in primary biliary cirrhosis. Confocal microscopy was used to quantify the intensity of fluorescence resulting from binding of fluorochrome-labeled antibody. In both liver and salivary glands MCA151A binding was similar in normal and sections with primary biliary cirrhosis and corresponded to the predicted distribution of mitochondria in these tissues. In the liver staining was less intense in biliary epithelial cells than in hepatocytes. In salivary gland binding of both antibodies was predominantly localized to duct cells, with those forming striated ducts, known to be rich in mitochondria, being most intensely stained. There was high coincidence of the two antigens in salivary glands (p < 0.01) and in biliary epithelial cells from normal liver (p = 0.01). However, in liver with primary biliary cirrhosis, despite high coincidence between the antigens on hepatocytes, biliary epithelial cells showed high intensity of pyruvate dehydrogenase dihydrolipoamide acetyltransferase but not MCA151A.(ABSTRACT TRUNCATED AT 250 WORDS)
Joplin
R E
RE
Liver Unit, Queen Elizabeth Hospital, Birmingham, United Kingdom.
Johnson
G D
GD
Matthews
J B
JB
Hamburger
J
J
Lindsay
J G
JG
Hubscher
S G
SG
Strain
A J
AJ
Neuberger
J M
JM
D000911:Antibodies, Monoclonal / Q000276:immunology; D001324:Autoantigens / Q000032:analysis*; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology* / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D004848:Epithelium / Q000201:enzymology / Q000276:immunology; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology* / Q000276:immunology; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000201:enzymology / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000032:analysis*; D012469:Salivary Glands / Q000201:enzymology* / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D015415:Biomarkers; D011768:Pyruvate Dehydrogenase Complex; D051047:Dihydrolipoyllysine-Residue Acetyltransferase