Immunochemical and functional properties of biliary alpha-1-antitrypsin.
Alpha-1-antitrypsin (AAT), the archetype of the serpin (serine proteinase inhibitor) superfamily, is synthesized by hepatocytes and excreted to some extent into bile. The role of intact biliary AAT in gallstone pathogenesis is unsettled, but its 36-residue C-terminal peptide was found to promote cholesterol crystallization in a bile model. The present study showed biliary AAT to have specific properties that differ from serum AAT regarding immunoreactivity, heat stability and antiproteolytical activity. Electrophoretical and immunochemical methods were used to characterize biliary AAT. The level of its inhibitory activity was determined spectrophotometrically. In 18 samples from common bile duct and 12 samples from gallbladder bile, AAT was found to be heat-stable and functionally inactive. Added to the untreated, temperature-inactivated or protease inhibitors containing bile, native AAT became functionally inactive, heat-stable and lost its immunoreactivity. In contrast, heat-inactivated AAT, native albumin, transferrin, alpha-1-antichymotrypsin and IgG were unaffected on being added to bile. AAT in human bile manifests specific biochemical properties, such as functional inactivity and heat stability, that may be consistent with a conformational transition of the serpin molecule induced by the hydrophobic environment, and which must be considered when evaluating its role in gallstone pathogenesis.
Janciauskiene
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Department of Medicine, University Hospital, Malmö, Sweden.
Toth
E
E
Sahlin
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Eriksson
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001646:Bile / Q000737:chemistry*; D015153:Blotting, Western; D004355:Drug Stability; D005260:Female; D006358:Hot Temperature; D006801:Humans; D015151:Immunoblotting; D007122:Immunoelectrophoresis; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*
D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin