A carcinoembryonic antigen (CEA) binding protein from ascites influences CEA uptake by macrophages.
A variant of CEA which is less readily endocytosed by macrophages has been isolated from malignant ascites. In vivo, CEA is cleared more slowly by the liver (t1/2 = 15.1 minutes) than CEAs isolated from hepatic metastases (t1/2 = 3.1 minutes). In vitro, rat and human Kupffer cells and rat alveolar macrophages endocytose this CEA less effectively. This slow clearing form of CEA is associated with a smaller (45kD) acidic glycoprotein (CORA) with which it forms a stable complex. CORA can be visualized on reducing gels but not on non reducing gels or by HPLC run under non reducing conditions. This suggests a non-covalent complex between the two glycoproteins. Analysis of protein conformation by circular dichroism revealed changes in the ascites CEA consistent with binding of CORA to the molecule. Western blot showed that CORA crossreacts with antisera to alpha 1-acid glycoprotein and double immunodiffusion demonstrated cross-reactivity but not identify. Sequencing of CNBr peptides showed sequence homology with alpha 1-acid glycoprotein but areas of unique sequence were also found. It is suggested that binding of CORA to CEA blocks the macrophage receptor binding of CEA.
Toth
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Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02115.
Steele
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Thomas
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D000595:Amino Acid Sequence; D000818:Animals; D001201:Ascites / Q000276:immunology*; D001693:Biological Transport, Active; D002272:Carcinoembryonic Antigen / Q000235:genetics / Q000302:isolation & purification; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism*; D002942:Circular Dichroism; D003110:Colonic Neoplasms / Q000276:immunology; D004705:Endocytosis; D006801:Humans; D007728:Kupffer Cells / Q000276:immunology; D008099:Liver / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000556:secondary; D008264:Macrophages / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D009961:Orosomucoid / Q000235:genetics; D010449:Peptide Mapping; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface; D012004:Rectal Neoplasms / Q000276:immunology; D012689:Sequence Homology, Nucleic Acid
D002272:Carcinoembryonic Antigen; D002352:Carrier Proteins; D009961:Orosomucoid; D011956:Receptors, Cell Surface; C065686:carcinoembryonic antigen binding protein, human