The effects of triton WR1339 and asialo-fetuin on the hepatic uptake of circulating native and asialo-carcinoembryonic antigen

Thomas, Peter; Jones, Michael E.

doi:10.1042/bj1730981

Cited by 10 publications

(3 citation statements)

References 11 publications

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“…The clearance of intravenously injected enterokinase in this study was found to be similar to that described for the removal of other human glycoproteins such as carcinoembryonic antigen (Thomas & Jones, 1978), lymphoblastoid interferon (Bose & Hickman, 1977) and lactoferrin (Prieels et al, 1978). Clearance was rapid, with a serum half-life of only 2.5min and was not due to active-site recognition.…”

Section: Discussionsupporting

confidence: 82%

“…700-fold molar excess over enterokinase) and aggregated human immunoglobulin (approx. 2 x 104-fold molar excess) have been shown to be bound preferentially by Kupffer cells (Thomas & Jones, 1978;Embling et al, 1978). Asialoagalacto-fetuin (2.2x 10'-fold molar excess) contained terminal N-acetylglucosamine residues, since it was isolated by lectin-specific affinity chromatography, and glycoproteins containing this determinant have also been shown to be taken up by phagocytic cells (Stahl et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of a defence mechanism in vivo against the leakage of enterokinase into the blood

Grant¹,

Magee²,

Meeks³

et al. 1979

Biochemical Journal

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1. The serum proteinase inhibitors alpha 1-antitrypsin, alpha 2-macroglobulin, inter-alpha-trypsin inhibitor and C1-esterase inhibitor were found not to affect the catalytic activity of human enterokinase, whereas bovine trypsin activity was modified essentially as expected. Enterokinase was also not inhibited by Trasylol (trypsin inhibitor from bovine lung) or bovine pancreatic trypsin inhibitor. No other component in human or mouse serum complexing with enterokinase was identified. 2. Human enterokinase administered intravenously into mice was rapidly cleared from the circulation with a half-life of 2.5 min. This removal was not the result of the difference in species, since partially purified mouse enterokinase was cleared at the same rate as the human enzyme. Clearance was mediated by recognition of the carbohydrate portion of enterokinase and not through specific recognition of its catalytic site. Immunofluorescent staining showed that the enzyme accumulated in the liver. Attempts to block the clearance by the simultaneous infusion of competing glycoproteins suggested that enterokinase was taken up by hepatocytes. Of the glycoproteins tested only two, human lactoferrin (terminal fucosyl alpha 1 leads to 3 N-acetylglucosamine) and bovine asialo-fetuin (terminal galactosyl beta 1 leads to 4 N-acetylglucosamine) were weakly competitive. Two inhibitors of endocytosis, Intralipid and Triton WR1339, failed to delay the removal of enterokinase. It is proposed that enterokinase is cleared from the circulation by an as yet uncharacterized hepatocyte receptor.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Identification of a defence mechanism in vivo against the leakage of enterokinase into the blood

Grant¹,

Magee²,

Meeks³

et al. 1979

Biochemical Journal

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“…Competitive-inhibition studies with yeast mannan (terminal mannose), agalacto-orosomucoid (terminal N-acetylglucosamine) and ,B-glucuronidase (terminal mannose) showed that these compounds failed to inhibit carcinoembryonic antigen uptake in vivo (Table 1). Asialo-(carcinoembryonic antigen) is cleared from the circulation by the hepatocyte receptor for galactose (Thomas & Jones, 1978). Since native carcinoembryonic antigen was taken up by the Kupffer cell exclusively, and competition in vivo with asialofetuin (terminal galactose) failed to inhibit this process (Table 1) Time (min) Fig.…”

Section: Resultsmentioning

confidence: 99%

A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat

Toth¹,

Thomas²,

Broitman³

et al. 1982

Biochemical Journal

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Native human carcinoembryonic antigen is rapidly removed from the circulation by the rat liver Kupffer cell after intravenous injection. The molecule is subsequently transferred to the hepatocyte in an immunologically identifiable form. Carcinoembryonic antigen has a circulatory half-life of 3.7 (+/- 0.8) min, and cellular entry is by receptor-mediated endocytosis. Non-specific fluid pinocytosis and phagocytosis can be excluded as possible mechanisms by the kinetics of clearance and failure of colloidal carbon to inhibit uptake. Substances with known affinity for the hepatic receptors for mannose, N-acetylglucosamine, fucose and galactose all fail to inhibit carcinoembryonic antigen clearance. After two cycles of the Smith degradation, carcinoembryonic antigen is still able to inhibit clearance of the native molecule. Receptor specificity is apparently not dependent on those non-reducing terminal sugars of the native molecule. Performic acid-oxidized carcinoembryonic antigen also inhibits clearance of carcinoembryonic antigen in vivo. Receptor binding is not dependent on tertiary protein conformation. Non-specific cross-reacting antigen, a glycoprotein structurally similar to carcinoembryonic antigen, is cleared by the same mechanism.

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Immunocytochemical staining for CEA in small cell carcinoma of lung predicts clinical usefulness of the plasma assay

Goslin

O’Brien

Skarin

et al. 1983

Cancer

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Recent studies have shown plasma CEA levels are useful in both staging and monitoring response to treatment in patients with small cell cancer of the lung (SCCL). CEA elevations do not occur in all patients however, and have been of less value in patients with limited disease. Immunoperoxidase staining for CEA performed on tumor tissue from 48 patients (17 extensive, 31 limited disease) with SCCL revealed: (1) A strong correlation between positive CEA tissue staining and plasma CEA elevation. Plasma CEA elevations occurred in 18/21 CEA tissue positive patients and correlated with the clinical course in all 18. In contrast elevated plasma CEAs were seen in only 3/27 CEA tissue negative patients; (2) CEA tissue positive patients had a higher incidence of extensive disease (62% versus 18%) and a higher incidence of liver metastases (43% versus 7%); and (3) No correlation between histologic subtype and CEA tissue staining was apparent. Cancer 52:301‐306, 1983.

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The effects of triton WR1339 and asialo-fetuin on the hepatic uptake of circulating native and asialo-carcinoembryonic antigen

Cited by 10 publications

References 11 publications

Identification of a defence mechanism in vivo against the leakage of enterokinase into the blood

Identification of a defence mechanism in vivo against the leakage of enterokinase into the blood

A new Kupffer cell receptor mediating plasma clearance of carcinoembryonic antigen by the rat

Immunocytochemical staining for CEA in small cell carcinoma of lung predicts clinical usefulness of the plasma assay

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