Fibronectin in human gallbladder bile: cholesterol pronucleating and/or mucin "link" protein?

Abstract

Some biliary proteins (pronucleators) seem to be essential factors for cholesterol crystal formation and crystal growth in bile. A recent study suggests that fibronectin is such a pronucleator in bile. Fibronectin also seems to closely interact with intestinal mucin. Since biliary mucin plays an important role in gallstone formation, such an interaction in bile may be of relevance in cholesterol gallstone formation. To more clearly elucidate the role of fibronectin in cholesterol gallstone disease, we measured the concentration of fibronectin in native bile of cholesterol gallstone patients and checked its influence on the cholesterol nucleation time of model bile. We further looked for a molecular interaction between biliary fibronectin and gallbladder mucin. We found that fibronectin is present in gallbladder bile of gallstone patients in low concentrations (2.6 +/- 1.2 micrograms/ml). Bile fibronectin did not interact with gallbladder mucin. Moreover, in a wide range of concentrations fibronectin had no influence on the nucleation time of model bile. We conclude that fibronectin does not seem to play a major role in cholesterol gallstone disease.

Mycobacterium aviumsubsp.paratuberculosisFibronectin Attachment Protein Facilitates M-Cell Targeting and Invasion through a Fibronectin Bridge with Host Integrins

“…The concentration of FN used to opsonize M. avium subsp. paratuberculosis in this investigation (2 g/ml) is equivalent to those reported for human bile (2 to 26 g/ml) (21,40). Hence, we believe that the use of FN-opsonized organisms in this investigation more closely resembles the situation in natural infections.…”

No pathophysiologic relationship of soluble biliary proteins to cholesterol crystallization in human bile

“…Our results show that the soluble glycoprotein mass recovered from the Con A column was 33 Ϯ 15% of total biliary proteins comparable to the modified method (36%) of Harvey, Upadhya, and Strasberg (27). In the literature, final concentrations of added Con A-binding glycoproteins ranged from 0.25 to 2 mg/mL (19,20,27). We added a final protein concentration of 1 mg/mL, which was similar to the pathophysiological levels in the gallbladder biles used in this study.…”

“…Abei et al (17) reported that ␣1-acid glycoprotein accounted for up to 30% of total accelerating activity in terms of ChM crystal detection times, however, De Bruijn and colleagues (19) could not find any pro-nucleating/ crystallizing activity with ␣1-acid glycoprotein. Chijiiwa et al (14) proposed that fibronectin, also a Con A-binding protein, was a pro-nucleating/crystallizing factor; whereas, two other groups (20,21) obtained results inconsistent with any nucleation/crystallization activity of fibronectin on ChM crystal detection times. In the extensive literature (summarized in ref.…”

“…Although it is highly likely (2-6) that mucin gel is a strong pro-nucleation/crystallization factor in lithogenic biles, the pathophysiological role, if any, of soluble biliary glycoproteins in the pathogenesis of Ch gallstone formation remains unclear. A large number of workers (7)(8)(9)(10)(11)(12)(13)(14)(15)(16) have demonstrated that soluble biliary glycoproteins could be pro-nucleating/crystallizing factors although this has been challenged by other reports (17)(18)(19)(20) suggesting that these glycoproteins have no effects on ChM crystal detection times in bile. Proteolysis of soluble biliary glycoproteins (21) does not influence the speed of ChM crystal detection either in normal or abnormal gallbladder and hepatic biles, which suggests that soluble biliary proteins may not be important pathophysiological factors affecting Ch crystallization (21).…”

Cholesterol crystal binding of biliary immuno-globulin A: visualization by fluorescence light microscopy

“…Besides cholesterol supersaturation [4] and gallbladder hypomotility [2,5] , kinetic protein factors that promote or inhibit cholesterol crystallization have been suggested to play key roles in cholesterol gallstone pathogenesis [6,7] . During the past decade, model bile studies indicated that several promoter or inhibitor proteins influence cholesterol crystallization in vitro [8][9][10][11][12][13][14] . Immunoglobulins were also identified as nucleating proteins in the gallbladder bile of patients with cholesterol gallstones [15,16] .…”