Lipopolysaccharides and Beta-Glucuronidase Activity in Choledochal Bile in Relation to Choledocholithiasis

Abstract

Common duct gallstones are mainly of the brown pigment type, which are usually attributed to bacterial factors. Bacterial β-glucuronidase most probably plays a role in the pathogenesis in many but not all patients. The role of other bacterial factors is more undecided. The aims of this study were to investigate a possible association between lipopolysaccharides (LPS) and choledocholithiasis, and to examine the interrelationship to β-glucuronidase. Common duct bile obtained at endoscopic retrograde cholangiography in 86 patients was assayed for LPS by a limulus amebocyte lysate test, and β-glucuronidase activity at pH 7.0 was measured. We found that both elevated concentration of LPS and the presence of juxtapapillary duodenal diverticula were associated with common duct stones (p < 0.01, both). Patients who had their common duct stones removed recently had a lower LPS concentration and a lower activity of β-glucuronidase than those who had a stone in situ (p < 0.01 both), but still higher LPS concentration than those without choledocholithiasis at all (p < 0.01). In multiple logistic regression analysis, elevated LPS was the significant predictor of common duct stones (p < 0.01), and not confounding with neither β-glucuronidase nor juxtapapillary diverticula. We conclude that gram-negative bacteria convey bacterial factors associated with choledocholithiasis, by mechanisms independent of, and additional to β-glucuronidase.

Lipopolysaccharide Activates Nuclear Factor-KappaB through Toll-Like Receptors and Related Molecules in Cultured Biliary Epithelial Cells

“…Similar processes using TLR may be operative in the biliary tree. In ascending cholangitis, pathogenic bacteria and their components in bile may elicit acute inflammation and induce secretion of proinflammatory cytokines by BEC (Liu et al, 1998;Matsumoto et al, 1994;Osnes et al, 1997;Yasoshima et al, 1998). It was shown in the current study that LPS or endotoxin was detected, and not infrequently, in normal gallbladder and cholecystolithiasis bile.…”

“…There have been several reports that bacterial components such as LPS, LTA, and bacterial DNA fragments are detectable in normal and pathologic bile (Hiramatsu et al, 2000;Osnes et al, 1997;Sasatomi et al, 1998), suggesting that BECs are exposed to bacterial components. Recently, BECs were shown to secrete polymeric IgA and also lactoferrin into bile, thereby contributing to the biliary mucosal defense (Saito and Nakanuma, 1992;Sugiura and Nakanuma, 1989).…”

Simultaneous, two-color fluorescence detection of total protein profiles and β-glucuronidase activity in polyacrylamide gel

“…Many commercially available test kits for water and foodstuffs use b-glucuronidase activity to quantify contamination by Escherichia coli and b-galactosidase activity to measure the presence of other coliform bacteria [7]. Bacterial b-glucuronidase has been implicated in human disease as playing a role in the pathogenesis of common duct gallstones [8]. Measurement of endogenous human b-glucuronidase activity is relevant to the evaluation of mucopolysaccharidosis type VII (Sly syndrome), a lysosomal storage disease caused by inherited deficiency of b-glucuronidase [9][10][11][12].…”

Lipopolysaccharide Initiates a Positive Feedback of Epidermal Growth Factor Receptor Signaling by Prostaglandin E2 in Human Biliary Carcinoma Cells

“…In inflammatory biliary tract diseases and associated carcinomas, the epithelium is exposed to high concentrations of LPS (14,16,17). We hypothesized that the exposure of some biliary epithelial cells to LPS initiates a signaling cascade leading to EGFR activation, which subsequently induces COX-2-dependent PGE 2 production, resulting in a second phase of EGFR activation, reinforcing and amplifying LPS-induced signaling (a positive feedback loop).…”