title: Surface alpha 2-3- and alpha 2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis.
abstract: 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 alpha 2-3-sialylated O-glycans and alpha 2-6- and alpha 2-3-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 alpha 2-6-sialylated N-glycans; ST3Gal1 contributes for the alpha2-3-sialylation of O-glycans, particularly T antigens; and ST3Gal4 may contribute for the increased alpha2-3-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.
authors: Departamento de Imunologia FCM-UNL, Campo Mártires da Pátria 130, 1169-056,, Lisbon, Portugal. pvideira.imuno@fcm.unl.pt
authors: Paula A
authors: PA
authors: Videira
authors: Inês F
authors: IF
authors: Amado
authors: Hélio J
authors: HJ
authors: Crespo
authors: M Carmen
authors: MC
authors: Algueró
authors: Fabio
authors: F
authors: Dall'Olio
authors: M Guadalupe
authors: MG
authors: Cabral
authors: Hélder
authors: H
authors: Trindade
mesh_terms: D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism*; D004705:Endocytosis; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism
chemical_list: D012799:Sialyltransferases; D019158:N-Acetylneuraminic Acid