The Sda antigen and its biosynthetic enzyme: differentiation-dependent and onco-developmentally regulated expression

Abstract

The blood group Sda antigen is a carbohydrate structure inherited as a dominant character and the β-linked N-acetylgalactosamine is the immunodominant sugar. This antigen is not confined to red cells but is mainly present in colon and kidney and is excreted in urine associated with the Tamm-Horsfall glycoprotein. A pentasaccharide fragment isolated from the Tamm-Horsfall glycoprotein with the GalNAcβ1,4 (NeuAcα2,3)Galβ1,4GlcNAcβ1,3Gal structure was found to have a very high Sdaactivity. The β1,-4-N-acetylgalactosaminyl-transferase involved in the biosynthesis of the Sda antigen (Sda-βGalNAc-transferase) strictly requires in acceptors a terminal galactose residue substituted at the 0-3 position with W-acetylneuraminic acid. The tissue distribution of this enzyme correlates with the predominant localization of Sda antigen in kidney and colon. The Sda-βGalNAc-transferase is practically absent in neonatal guinea-pig kidney and in large intestine of suckling rat and is dramatically reduced in human colon carcinomas indicating that the expression is onco-developmentally regulated. In human colon carcinoma cells in culture only Caco-2 cells express the Sda-βGalNAc-transferase at a level that parallels the degree of enterocyte differentiation. A large amount of the enzyme is released in the soluble form by differentiated Caco-2 cells, preferentially from the basolateral face. One may postulate that a reduced susceptibility to infections caused by enterotoxigenic and pyelonephritogenic Escherichia coli strains which specifically bind to the NeuAcα2,3Galβ-units has been the selective agent responsible for the dominant expression of the Sda-βGalNAc-transferase in distal kidney and colon.