Human Gallstones Contain Pronucleating Nonmucin Glycoproteins That are Immunoglobulins

Lipsett, Pamela A.; Hildreth, James E. K.; Kaufman, Howards S.; Lillemoe, Keith D.; Pitt, Henry A.

doi:10.1097/00000658-199401000-00005

Cited by 16 publications

(5 citation statements)

References 24 publications

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“…These glycoproteins include mucin glycoproteins, which are the most abundant, and nonmucin glycoproteins, such as aminopeptidase N, α2-macroglobulin, hemopexin, immunoglobulin heavy chains, and the β-chain of haptoglobulin (Klinkspoor et al 1994; Lipsett et al 1994; Offner et al 1994; van Wijland et al 1994; Busch et al 1995). These glycoproteins play important roles in protection against the detergent action of bile salts under physiological conditions, and in cholesterol crystallization under pathological conditions (Klinkspoor et al 1994; Lipsett et al 1994; Offner et al 1994; van Wijland et al 1994; Busch et al 1995). Likewise, Hakata antigen may associate with these glycoproteins in bile and may affect the activities of these glycoproteins.…”

Section: Discussionmentioning

confidence: 99%

Hakata Antigen, a New Member of the Ficolin/Opsonin p35 Family, Is a Novel Human Lectin Secreted into Bronchus/Alveolus and Bile

Akaiwa

Yae

Sugimoto

et al. 1999

J Histochem Cytochem.

116

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SUMMARYHakata antigen was first reported as a serum protein that reacted with an autoantibody from patients with systemic lupus erythematosus. Recently, it has been found that Hakata antigen is a new member of the ficolin/opsonin p35 family, which is a distinct lectin family, on the basis of homology of structures and the common characteristic of possessing lectin activity. In this study we analyzed the tissue distribution of Hakata antigen. Hakata antigen mRNA and protein were generated in the lung and liver. In the lung, Hakata antigen was produced by both ciliated bronchial epithelial cells and Type II alveolar epithelial cells and was secreted into the bronchus and alveolus. In the liver, Hakata antigen was produced by bile duct epithelial cells and hepatocytes and was also secreted into the bile duct. These results demonstrate that Hakata antigen is a unique lectin protein that exists not only in serum but also in bronchus/alveolus and bile, and indicate that Hakata antigen plays a role in bronchus/alveolus and bile under physiological conditions. H akata antigen was first reported by Inaba and Okochi (1978) as a serum protein that reacted with an autoantibody from patients with systemic lupus erythematosus (SLE). Since then, it has been demonstrated that Hakata antigen is a novel thermolabile ␤ 2-macroglycoprotein that exists as a monomer of 35 kD in reducing conditions and as a huge homopolymer of 650 kD in serum or in nonreducing conditions (Yae et al. 1991). All sera from 10,050 healthy Japanese donors, 99.99% of 751,352 Japanese outpatients, and 99.98% of 41,430 Swedish outpatients contained Hakata antigen, showing that Hakata antigen is a normal serum constituent (Inaba et al. 1990). The range of Hakata antigen in serum was 7-23 g/ ml (Yae et al. 1991).We have recently identified the cDNA encoding Hakata antigen, revealing that Hakata antigen consists of a collagen-like domain in the middle section and a fibrinogen-like domain in the C terminus, both of which are homologous to two lectin activity-possessing proteins, human ficolin-1 and opsonin p35 (Sugimoto et al. 1998). Homologies between Hakata antigen and either human ficolin-1 or opsonin P35 were both 48% overall, higher in the collagen-like domain (48%, 54%) and in the fibrinogen-like domain (52%, 53%), respectively (Sugimoto et al. 1998). We have further demonstrated that purified Hakata antigen sustains lectin activity, showing affinity with GalNac, GlcNac, and d -fucose as mono/oligosaccharide, and LPSs from Salmonella typhimurium and S. minnesota (Sugimoto et al. 1998). These three molecules apparently form a distinct human lectin family. However, the physiological roles of these related molecules have remained unresolved. To date, porcine and mouse homologues of human ficolin-1 and opsonin p35 have been identified, whereas that of Hakata antigen has not been found (Ichijo et al.

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Section: Discussionmentioning

confidence: 99%

Hakata Antigen, a New Member of the Ficolin/Opsonin p35 Family, Is a Novel Human Lectin Secreted into Bronchus/Alveolus and Bile

Akaiwa

Yae

Sugimoto

et al. 1999

J Histochem Cytochem.

116

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“…Indeed, Fab fragments isolated from patients with cholesterol gallstones accelerated cholesterol crystal observation times in vitro, whereas commercially available Fab fragments did not 73. These data indicate that antigen-specific Fab fragments might contribute to cholesterol nucleation in vitro 73. Therefore, merely quantifying Ig concentrations in bile appears to provide limited functional information.…”

Section: Role Of Infection Inflammation and The Immune System In Fomentioning

confidence: 98%

Roles of Infection, Inflammation, and the Immune System in Cholesterol Gallstone Formation

2009

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Cholesterol gallstone formation is a complex process mediated by genetic and environmental factors. Until recently, the role of the immune system in the pathogenesis of cholesterol gallstones was not considered a valid topic of research interest. This review collates and interprets an extensive body of basic literature, some of which is not customarily considered to be related to cholelithogenesis, describing the multiple facets of the immune system that appear to be involved in cholesterol cholelithogenesis. A thorough understanding of the immune interactions with biliary lipids and cholecystocytes should modify current views of the pathogenesis of cholesterol gallstones, promote further research on the pathways involved, and lead to novel diagnostic tools, treatments, and preventive measures.Bile is a complex aqueous colloidal system that is essential for a wide range of physiologic functions, including the excretion of lipids from the organism and intestinal fat absorption. 1,2 Bile is formed primarily in hepatic canaliculi, small (1-2 μm) spaces formed between the tight junctions of hepatocytes. It is composed of water, electrolytes, and a variety of lipid solutes dispersed in mixed micelles and vesicles including bile salts, phospholipids (>96% being mixed phosphatidylcholines), and cholesterol, as well as proteins and bilirubin conjugates. 3 Phospholipids and bile salts are essential for the removal from the organism of otherwise insoluble cholesterol molecules in an aqueous environment by solubilizing the sterol in mixed micelles, composed of the catabolic product bile salts, and unilamellar vesicles. [2][3][4] Bile is transported from the canaliculi along tubules of increasingly greater diameter until it egresses into the gut at the midduodenum. In health, about half the secreted bile is stored, concentrated, and slightly acidified in the gallbladder during the interdigestive interval. The gallbladder is connected to the biliary tree via the cystic duct, which functions simultaneously as a gallbladder filling and emptying conduit. 3 Alterations in the relative or absolute proportions of cholesterol, phospholipids, and bile salts can lead to phase separation of cholesterol from solution in bile. Most frequently these changes Address requests for reprints to: Kirk J. Maurer, DVM, PhD, Cornell Center for Animal Resources and Education, College of Veterinary Medicine, Cornell University, Ithaca, New York. e-mail: km429@cornell.edu; fax: (607) 253-3527. M.C.C. and J.G.F. contributed equally to this work. John P. Lynch and David C. Metz, Section EditorsThe authors disclose no conflicts. NIH Public Access Author ManuscriptGastroenterology. Author manuscript; available in PMC 2010 February 1. Published in final edited form as:Gastroenterology. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript result from excess secretion of cholesterol from the liver. [1][2][3] As the absolute cholesterol concentration increases, the excess cholesterol phase separates, forming unilamellar vesicle...

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“…In addition to a radiating, scaffolding matrix containing also Ca phosphates (Sutor and Wooley, 1974), other peculiar macromolecular co-aggregates of peculiar sterols have been detected, e.g., sapogenins, in the form of diosgenin salts (Gilloteaux et al, manuscript in preparation;Troxler, 1986) as well as, surprisingly, silicium salts. The nuclei of gallstones are known to be rich in proteinaceous compounds (e.g., immunoglobulins: Afdhal et al, 1990;Delacroix, 1985;Delacroix et al, 1982;Dive, 1970;Harvey et al, 1991;Lipsett et al, 1994) and scanning microscopic aspects of cores of cholesterol, mixed and pigment stones have been reported (Gilloteaux et al, 1991).…”

Section: Gallstonesmentioning

confidence: 99%

Comparative morphology of the gallbladder and biliary tract in vertebrates: Variation in structure, homology in function and gallstones

Oldham-Ott

Gilloteaux

1997

Microsc. Res. Tech.

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Human Gallstones Contain Pronucleating Nonmucin Glycoproteins That are Immunoglobulins

Cited by 16 publications

References 24 publications

Hakata Antigen, a New Member of the Ficolin/Opsonin p35 Family, Is a Novel Human Lectin Secreted into Bronchus/Alveolus and Bile

Hakata Antigen, a New Member of the Ficolin/Opsonin p35 Family, Is a Novel Human Lectin Secreted into Bronchus/Alveolus and Bile

Roles of Infection, Inflammation, and the Immune System in Cholesterol Gallstone Formation

Comparative morphology of the gallbladder and biliary tract in vertebrates: Variation in structure, homology in function and gallstones

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