Volume 11, Issue 4 pp. 525-533
Original Article
Free Access

Isolation of a potent cholesterol nucleation-promoting activity from human gallbladder bile: Role in the pathogenesis of gallstone disease

Dr. Albert K. Groen

Corresponding Author

Dr. Albert K. Groen

Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

Department of Gastroenterology and Hepatology, FO-116, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands===Search for more papers by this author
Christa Noordam

Christa Noordam

Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

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Jan A. G. Drapers

Jan A. G. Drapers

Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

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Peter Egbers

Peter Egbers

Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

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Peter L. M. Jansen

Peter L. M. Jansen

Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

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Guido N. J. Tytgat

Guido N. J. Tytgat

Department of Gastroenterology and Hepatology, Academic Medical Center, 1105 AZ Amsterdam, The Netherlands

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First published: April 1990
Citations: 101

This work was presented in part in abstract formj at the annual meeting of the American Association for the study of Liver Diseases, Chicago, Illinois, October 1987

Abstract

Gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity was found in gallbladder bile from cholesterol gallstone patients but also in gallbladder bile from patients without stones and patients with pigment stones. Bile from patients with multiple cholesterol gallstones contained high concanavalin A-binding nucleation-promoting activity. The activity was much lower in bile samples from pigment stone patients, patients without stones and patients with a solitary cholesterol stone. Serum contained very little activity and no concanavalin A-binding nucleation-promoting activity could be demonstrated in gallbladder mucosa. This suggests that concanavalin A-binding nucleation promoter is produced in the liver or bile duct epithelium. The activity was fully resistant to digestion with pronase but was heat labile and could be destroyed by prolonged incubation with a mixed gly cosidase preparation indicating that sugar residues are important for this activity. On a Superose 12 gel permeation column, promoting activity eluted in two major peaks at apparent molecular weights of 150 ± 30 kD (n = 5) and < 5 kD respectively. The mobility on the column was not int influenced by pronase digestion. The factor with the higher molecular weight could be isolated further by polyacrylamide gel electrophoresis under nondenaturing conditions. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the apparent molecular weight of the glycoprotein was 130 kD. In conclusion, gallbladder bile contains nucleation-promoting activity that binds to concanavalin A. The activity is increased in bile from patients with multiple cholesterol gallstones and could therefore play an important role in the pathogenesis of gallstone disease.(HEPATOLOGY 1990; 11:525:533.)

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