S. Janciauskiene et al., IMMUNOCHEMICAL AND FUNCTIONAL-PROPERTIES OF BILIARY ALPHA-1-ANTITRYPSIN, Scandinavian journal of clinical & laboratory investigation, 56(7), 1996, pp. 597-608
Alpha-1-antitrypsin (AAT), the archetype of the serpin (serine protein
ase 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 pres
ent study showed biliary AAT to have specific properties that differ f
rom serum AAT regarding immunoreactivity, heat stability and anti-prot
eolytical 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-s
table and functionally inactive. Added to the untreated, temperature-i
nactivated or protease inhibitors containing bile, native AAT became f
unctionally inactive, heat-stable and lost its immunoreactivity. In co
ntrast, heat-inactivated AAT, native albumin, transferrin, alpha-1-ant
ichymotrypsin and IgG were unaffected on being added to bile. AAT in h
uman bile manifests specific biochemical properties, such as functiona
l inactivity and heat stability, that may be consistent with a conform
ational transition of the serpin molecule induced by the hydrophobic e
nvironment, and which must be considered when evaluating its role in g
allstone pathogenesis.