Groen A K
Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
Hepatology. 1990 Sep;12(3 Pt 2):189S-192S; discussion 192S-194S.
Cholesterol crystallization-promoting factors probably play an important role in the pathogenesis of gallstone disease. We have isolated one of the factors involved by using lectin-affinity chromatography. A potent promoting activity binds to concanavalin A-Sepharose. The activity is heat labile and sensitive to digestion by glycosidase but remarkably insensitive to proteases. The concanavalin A-binding pronucleator affects cholesterol solubilization in model bile in two ways. It induces a shift of cholesterol and phospholipid from the micellar to the vesicular phase but also interacts directly with cholesterol-phospholipid vesicles. The concanavalin A-binding protein fraction contains at least two different promoting factors with gel permeation molecular weights of about 150 kD and 5 kD, respectively. The higher molecular weight activity could be assigned to a protein with an apparent molecular weight of 130 kD. Concanavalin A-binding-promoting activity was present in bile from both patients with and without stones, indicating that it is a normal constituent of bile. However, the activity was strongly increased in bile from patients with multiple cholesterol gallstones, suggesting that it could play a key role in gallstone formation in these patients.
胆固醇结晶促进因子可能在胆石病的发病机制中起重要作用。我们通过凝集素亲和层析分离出了其中一种相关因子。一种强效促进活性与伴刀豆球蛋白A - 琼脂糖结合。该活性对热不稳定,对糖苷酶消化敏感,但对蛋白酶显著不敏感。伴刀豆球蛋白A结合的成核因子以两种方式影响模型胆汁中胆固醇的溶解。它诱导胆固醇和磷脂从胶束相转移到囊泡相,但也直接与胆固醇 - 磷脂囊泡相互作用。伴刀豆球蛋白A结合蛋白组分包含至少两种不同的促进因子,其凝胶渗透分子量分别约为150 kD和5 kD。较高分子量的活性可归因于一种表观分子量为130 kD的蛋白质。伴刀豆球蛋白A结合促进活性在有结石和无结石患者的胆汁中均存在,表明它是胆汁的正常成分。然而,在患有多发性胆固醇结石患者的胆汁中该活性显著增加,提示它可能在这些患者的胆结石形成中起关键作用。