Janciauskiene S, Toth E, Sahlin S, Eriksson S
Department of Medicine, University Hospital, Malmö, Sweden.
Scand J Clin Lab Invest. 1996 Nov;56(7):597-608. doi: 10.3109/00365519609090594.
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.
α1-抗胰蛋白酶（AAT）是丝氨酸蛋白酶抑制剂（serpin）超家族的原型，由肝细胞合成并部分排泄到胆汁中。完整的胆汁AAT在胆结石发病机制中的作用尚不清楚，但其36个残基的C末端肽在胆汁模型中可促进胆固醇结晶。本研究表明，胆汁AAT具有与血清AAT不同的特异性，包括免疫反应性、热稳定性和抗蛋白水解活性。采用电泳和免疫化学方法对胆汁AAT进行表征，通过分光光度法测定其抑制活性水平。在18份胆总管样本和12份胆囊胆汁样本中，发现AAT具有热稳定性且功能失活。将天然AAT添加到未处理的、经温度灭活的或含有蛋白酶抑制剂的胆汁中，AAT会变得功能失活、热稳定并失去免疫反应性。相比之下，热灭活的AAT、天然白蛋白、转铁蛋白、α1-抗糜蛋白酶和IgG添加到胆汁中时不受影响。人胆汁中的AAT表现出特定的生化特性，如功能失活和热稳定性，这可能与疏水环境诱导的丝氨酸蛋白酶抑制剂分子构象转变一致，在评估其在胆结石发病机制中的作用时必须予以考虑。
