1994 Fiscal Year Final Research Report Summary
Role of cholesterol crystallization-promoting protein in the pathogenesis of cholesterol gallstone.
| Project/Area Number |
05670445
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | University of Tsukuba |
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Principal Investigator |
TANAKA Naomi Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (60111530)
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| Co-Investigator(Kenkyū-buntansha) |
ABEO Masato Institute of Clinical Medicine, Assistant Professor, 臨床医学系, 講師 (20261802)
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| Project Period (FY) |
1993 – 1994
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| Keywords | gallstone / cholesterol / alpha_1-acid glycoprotein / nucleation / biliary protein / immunoglobulins / crystal growth |
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| Research Abstract |
Rapid cholesterol crystallization in bile is the critical event leading to cholesterol gallstone formation. Several glycoprotein promoters (immunoglobulins, phospholipase C,aminopeptidase N) of cholesterol crystallization have recently been reported in bile with gallstones, which have received world-wide attention. We have successfully isolated a new promoter and identified it as alpha_1-acid glycoprotein. However, no study compared these promoters in vitro and their precise role in the pathogenesis of gallstones remains unknown. Therefore, we aimed in this study to clarify the role of these cholesterol crystallization-promoters in the pathogenesis of gallstones. Firstly, the cholesterol crystallization-promoting activity of these glycoproteins was compared in vitro. It was found that only alpha_1-acid glycoprotein and immunoglobulins exsert the promoting activity at their physiologic levels in bile. Secondly, the biliary levels of alpha_1-acid glycoprotein in various gallstone and non-gallstone patients were assayd by a newly established specific ELISA and compared with the cholesterol nucleation time in bile. This revealed that the alpha_1-acid glycoprotein level is not altered in biles with solitary cholesterol or pigment gallstones but it is specifically elevated in biles with multiple cholesterol gallstones and that its increase is associated with rapid nucleation time. The potent promoting activity in vitro as well as the specific increase in bile (in vivo) with multiple cholesterol gallstones suggest the critical role of the biliary alpha_1-acid glycoprotein in the formation of multiple cholesterol gallstones.
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