EFFECT OF HETEROGENEITY OF CARCINOEMBRYONIC ANTIGEN ON LIVER-CELL MEMBRANE-BINDING AND ITS KINETICS OF REMOVAL FROM CIRCULATION

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (7) , 3137-3142
Abstract
Carcinoembryonic antigen (CEA) is a glycoprotein metabolized primarily by the liver. Subcellular fractions of rat liver were examined for CEA binding activity. Hepatocyte plasma membrane and microsome fractions bound CEA, and this binding shared the Ca requirement, neuraminidase sensitivity and carbohydrate specificity of the hepatocyte asialoglycoprotein receptor. CEA had previously been shown to react with this galactose-specific receptor, in vivo, only following neuraminidase treatment. Galactose receptor binding of CEA was measured in 3 different purified CEA preparations. The fraction of CEA capable of binding to excess levels of galactose receptor on membranes varied (46.5%, 40.2% and 4.7% for CEA-1, -2, and -3, respectively). These CEA were 2.3%, 7.9% and 0.7% as effective, respectively, as asialo-.alpha.1-acid glycoprotein in inhibiting the binding of radiolabeled asialo-.alpha.1-acid glycoprotein to liver cell membranes. Each of the 3 CEA preparations showed different clearance kinetics from the circulation of mice. Coinjection of asialo-.alpha.1-acid glycoprotein with the CEA revealed differing inhibition of the clearances. Differences in the carbohydrate components of purified CEA preparations affect their rate of removal from circulation and possibly the relationship between CEA production and observed plasma levels in patients. The possible origin of these CEA differences is discussed with their clinical implications.