Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: an immunohistochemical study.
The reason for the close association between primary biliary cirrhosis and the appearance of antibodies that recognize the E2 component of pyruvate dehydrogenase complex is not understood. The distribution of the three pyruvate dehydrogenase complex subunits was examined in the liver and lymph nodes of patients with primary biliary cirrhosis, patients with other liver diseases and normal subjects by immunohistochemistry using affinity-purified antibodies. Intensity of staining was assessed semiquantitatively and validated by scanning laser confocal microscopy. In primary biliary cirrhosis tissue, the E2 staining pattern did not parallel the reported distribution of mitochondria. E2 staining in biliary epithelial cells was consistently stronger than in hepatocytes. In primary biliary cirrhotic liver, staining of biliary epithelium was significantly stronger than in normal or other liver disease controls; many bile ducts in primary biliary cirrhotic liver demonstrated very high intensity, diffuse distribution of stain. No differences in staining intensity were seen between perivenular hepatocytes in primary biliary cirrhotic liver and those in controls; periportal hepatocytes in primary biliary cirrhotic liver were, however, more intensely stained than perivenular cells. In primary biliary cirrhotic portal lymph nodes, a subset of macrophages showed high-intensity, diffuse distribution of stain. By contrast, staining with antibodies to E1 and E3 (other components of pyruvate dehydrogenase complex) produced uniform-intensity, mitochondrial distribution both in primary biliary cirrhosis and control tissue. The increased intensity of E2 in primary biliary cirrhotic tissue could be explained in terms of abnormal metabolism of E2 by biliary epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Joplin
R
R
Department of Medicine, University of Birmingham/Liver Unit, Queen Elizabeth Medical Centre, United Kingdom.
Lindsay
J G
JG
Hubscher
S G
SG
Johnson
G D
GD
Shaw
J C
JC
Strain
A J
AJ
Neuberger
J M
JM
D000123:Acetyltransferases / Q000378:metabolism*; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000201:enzymology* / Q000473:pathology; D008198:Lymph Nodes / Q000201:enzymology* / Q000473:pathology; D011768:Pyruvate Dehydrogenase Complex; D013194:Staining and Labeling; D014018:Tissue Distribution
D011768:Pyruvate Dehydrogenase Complex; D000123:Acetyltransferases; D051047:Dihydrolipoyllysine-Residue Acetyltransferase