PMID- 18080182 OWN - NLM STAT- MEDLINE DCOM- 20080624 LR - 20220716 IS - 0282-0080 (Print) IS - 0282-0080 (Linking) VI - 25 IP - 3 DP - 2008 Apr TI - Surface alpha 2-3- and alpha 2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. PG - 259-68 AB - 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. FAU - Videira, Paula A AU - Videira PA AD - Departamento de Imunologia FCM-UNL, Campo Martires da Patria 130, 1169-056,, Lisbon, Portugal. pvideira.imuno@fcm.unl.pt FAU - Amado, Ines F AU - Amado IF FAU - Crespo, Helio J AU - Crespo HJ FAU - Alguero, M Carmen AU - Alguero MC FAU - Dall'Olio, Fabio AU - Dall'Olio F FAU - Cabral, M Guadalupe AU - Cabral MG FAU - Trindade, Helder AU - Trindade H LA - eng PT - Journal Article DEP - 20071213 PL - United States TA - Glycoconj J JT - Glycoconjugate journal JID - 8603310 RN - EC 2.4.99.- (Sialyltransferases) RN - GZP2782OP0 (N-Acetylneuraminic Acid) SB - IM MH - Cell Differentiation MH - Cell Membrane/*metabolism MH - Cells, Cultured MH - Dendritic Cells/*cytology/*metabolism MH - *Endocytosis MH - Gene Expression Regulation, Enzymologic MH - Humans MH - Monocytes/*cytology/*metabolism MH - N-Acetylneuraminic Acid/*metabolism MH - Sialyltransferases/genetics/metabolism EDAT- 2007/12/15 09:00 MHDA- 2008/06/25 09:00 CRDT- 2007/12/15 09:00 PHST- 2007/03/19 00:00 [received] PHST- 2007/11/15 00:00 [accepted] PHST- 2007/08/24 00:00 [revised] PHST- 2007/12/15 09:00 [pubmed] PHST- 2008/06/25 09:00 [medline] PHST- 2007/12/15 09:00 [entrez] AID - 10.1007/s10719-007-9092-6 [doi] PST - ppublish SO - Glycoconj J. 2008 Apr;25(3):259-68. doi: 10.1007/s10719-007-9092-6. Epub 2007 Dec 13.