The Sd^a Antigen and Its Biosynthetic Enzyme:

Differentiation-dependent and Onco-developmentally Regulated Expression

Abstract

The blood group Sd^a 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 Sd^a activity. The β1, 4-N-acetylgalactosaminyl-transferase involved in the biosynthesis of the Sd^a antigen (Sd^a-βGalNAc-transferase) strictly requires in acceptors a terminal galactose residue substituted at the O-3 position with N-acetylneuraminic acid. The tissue distribution of this enzyme correlates with the predominant localization of Sd^a antigen in kidney and colon. The Sd^a-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 Sd^a-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 Sd^a-βGalNAc-transferase in distal kidney and colon.