Surface [alpha]2-3- and [alpha]2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis

• Published in: Glycoconjugate journal Vol. 25; no. 3; p. 259
• Main Authors: Videira, Paula A, Amado, Inês F, Crespo, Hélio J, Algueró, M Carmen, Dall'olio, Fabio, Cabral, M Guadalupe, Trindade, Hélder
• Format: Journal Article
• Language: English
• Published: New York Springer Nature B.V 01-04-2008
• Subjects: Carbohydrates; Cellular biology; Endocytosis; Enzymes; Glycosylation; Immunotherapy
• ISSN: 0282-0080; 1573-4986
• DOI: 10.1007/s10719-007-9092-6

Several glycoconjugates are involved in the immune response. Sialic acid is frequently the glycan terminal sugar and it may modulate immune interactions. Dendritic cells (DCs) are antigen-presenting cells with high endocytic capacity and a central role in immune regulation. On this basis, DCs derived from monocytes (mo-DC) are utilised in immunotherapy, though many features are ignored and their use is still limited. We analyzed the surface sialylated glycans expressed during human mo-DC generation. This was monitored by lectin binding and analysis of sialyltransferases (ST) at the mRNA level and by specific enzymatic assays. We showed that α2-3-sialylated O-glycans and α2-6- and α2-3-sialylated N-glycans are present in monocytes and their expression increases during mo-DC differentiation. Three main ST genes are committed with this rearrangement: ST6Gal1 is specifically involved in the augmented α2-6-sialylated N-glycans; ST3Gal1 contributes for the α2-3-sialylation of O-glycans, particularly T antigens; and ST3Gal4 may contribute for the increased α2-3-sialylated N-glycans. Upon mo-DC maturation, ST6Gal1 and ST3Gal4 are downregulated and ST3Gal1 is altered in a stimulus-dependent manner. We also observed that removing surface sialic acid of immature mo-DC by neuraminidase significantly decreased its endocytic capacity, while it increased in monocytes. Our results indicate the STs expression modulates the increased expression of surface sialylated structures during mo-DC generation, which is probably related with changes in cell mechanisms. The ST downregulation after mo-DC maturation probably results in a decreased sialylation or sialylated glycoconjugates involved in the endocytosis, contributing to the downregulation of one or more antigen-uptake mechanisms specific of mo-DC. [PUBLICATION ABSTRACT]