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

Abstract

Native human carcinoembryonic antigen [CEA] is rapidly removed from the circulation by the rat liver Kupffer cell after i.v. injection. The molecule is subsequently transferred to the hepatocyte in an immunologically identifiable form. CEA 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 CEA clearance. After 2 cycles of the Smith degradation, CEA 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 CEA also inhibits clearance of CEA in vivo. Receptor binding is not dependent on tertiary protein conformation. Non-specific cross-reacting antigen, a glycoprotein structurally similar to CEA, is cleared by the same mechanism.