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Surface α2-3- and α2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis

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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 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.

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Abbreviations

DC:

Dendritic cell

Mo-DC:

monocyte derived DC

KO:

knockout

ST:

Sialyltransferase

SNA:

Sambucus nigra lectin

MAA:

Maackia amurensis lectin

PNA:

Arachis hypogaea lectin

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Acknowledgments

We thank Manuela Correia for her technical assistance with Real Time PCR and Glória Nunes with her help in flow cytometry.

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Authors and Affiliations

  1. Departamento de Imunologia FCM-UNL, Campo Mártires da Pátria 130, 1169-056,, Lisbon, Portugal

    Paula A. Videira, Inês F. Amado, Hélio J. Crespo, M. Carmen Algueró, M. Guadalupe Cabral & Hélder Trindade

  2. Dipartimento di Patologia Sperimentale, Via S. Giacomo 14, 40126, Bologna, Italy

    Fabio Dall’Olio

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  1. Paula A. Videira
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  2. Inês F. Amado
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Correspondence to Paula A. Videira.

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Videira, P.A., Amado, I.F., Crespo, H.J. et al. Surface α2-3- and α2-6-sialylation of human monocytes and derived dendritic cells and its influence on endocytosis. Glycoconj J 25, 259–268 (2008). https://doi.org/10.1007/s10719-007-9092-6

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  • DOI: https://doi.org/10.1007/s10719-007-9092-6

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