| Polysialylated neuropilin-2 enhances human dendritic cell migration through the basic C-terminal region of CCL21. | |
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MedLine Citation:
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PMID: 20488940 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Dendritic cell (DC) migration to secondary lymphoid organs is a critical step to properly exert its role in immunity and predominantly depends on the interaction of the chemokine receptor CCR7 with its ligands CCL21 and CCL19. Polysialic acid (PSA) has been recently reported to control CCL21-directed migration of mature DCs. Here, we first demonstrate that PSA present on human mature monocyte-derived dendritic cells did not enhance chemotactic responses to CCL19. We have also explored the molecular mechanisms underlying the selective enhancing effect of PSA on CCL21-driven chemotaxis of DCs. In this regard, we found out that prevention of DC polysialylation decreased CCL21 activation of JNK and Akt signaling pathways, both associated with CCR7-mediated chemotaxis. We also report that the enhanced PSA-mediated effect on DC migration towards CCL21 relied on the highly basic C-terminal region of this chemokine and depended on the PSA acceptor molecule neuropilin-2 (NRP2) and on the polysialyltransferase ST8SiaIV. Altogether, our data indicate that the CCR7/CCL21/NRP2/ST8SiaIV functional axis constitutes an important guidance clue for DC targeting to lymphoid organs. |
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Authors:
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Angela Rey-Gallardo; Cristina Escribano; Cristina Delgado-Martín; José L Rodriguez-Fernández; Rita Gerardy-Schahn; Urs Rutishauser; Angel L Corbi; Miguel A Vega |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-20 |
Journal Detail:
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Title: Glycobiology Volume: 20 ISSN: 1460-2423 ISO Abbreviation: Glycobiology Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-12-02 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9104124 Medline TA: Glycobiology Country: England |
Other Details:
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Languages: eng Pagination: 1139-46 Citation Subset: IM |
Affiliation:
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Departamento de Microbiología Molecular y Biología de las Infecciones, Centro de Investigaciones Biológicas, CSIC, Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Amino Acids, Basic / chemistry, metabolism Animals COS Cells Cell Movement / drug effects, genetics, physiology* Cells, Cultured Cercopithecus aethiops Chemokine CCL21 / chemistry*, metabolism*, pharmacology, physiology Dendritic Cells / drug effects, metabolism, physiology* Humans Models, Biological Molecular Sequence Data Neuropilin-2 / antagonists & inhibitors, genetics, metabolism*, physiology* Protein Interaction Domains and Motifs / drug effects, physiology Protein Processing, Post-Translational / physiology RNA, Small Interfering / pharmacology Sequence Homology, Amino Acid Sialic Acids / metabolism Up-Regulation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids, Basic; 0/CCL21 protein, human; 0/Chemokine CCL21; 0/Neuropilin-2; 0/RNA, Small Interfering; 0/Sialic Acids; 0/polysialic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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