Design of phosphorylated dendritic architectures to promote human monocyte activation

As first defensive line, monocytes are a pivotal cell population of innate immunity. Monocyte activation can be relevant to a range of immune conditions and responses. Here we present new insights into the activation of monocytes by a series of phosphonic acid-terminated, phosphorus-containing dendr...

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Published in:The FASEB journal 2006-11, Vol.20 (13), p.2339-2351
Main Authors: Poupot, Mary, Griffe, Laurent, Marchand, Patrice, Maraval, Alexandrine, Rolland, Olivier, Martinet, Ludovic, L'Faqihi-Olive, Fatima-Ezzahra, Turrin, Cédric-Olivier, Caminade, Anne-Marie, Fournié, Jean-Jacques, Majoral, Jean-Pierre, Poupot, Rémy
Format: Article
Language:English
Subjects:
Adult
Cell Culture Techniques
cellular immunotherapy
Dendrimers
Dendrimers - metabolism
Fluorescein-5-isothiocyanate
Hematology
Human health and pathology
Humans
Life Sciences
Monocytes
Monocytes - cytology
Monocytes - physiology
NF-kappa B
NF-kappa B - metabolism
Phagocytosis
Phosphorus
Phosphorus - metabolism
phosphorus dendrimers
Phosphorylation
Protein Transport
targeting
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Summary:As first defensive line, monocytes are a pivotal cell population of innate immunity. Monocyte activation can be relevant to a range of immune conditions and responses. Here we present new insights into the activation of monocytes by a series of phosphonic acid-terminated, phosphorus-containing dendrimers. Various dendritic or subdendritic structures were synthesized and tested, revealing the basic structural requirements for monocyte activation. We showed that multivalent character and phosphonic acid capping of dendrimers are crucial for monocyte targeting and activation. Confocal videomicroscopy showed that a fluorescein-tagged dendrimer binds to isolated monocytes and gets internalized within a few seconds. We also found that dendrimers follow the phagolysosomial route during internalization by monocytes. Finally, we performed fluorescence resonance energy transfer (FRET) experiments between a specifically designed fluorescent dendrimer and phycoerythrin-coupled antibodies. We showed that the typical innate Toll-like receptor (TLR)-2 is clearly involved, but not alone, in the sensing of dendrimers by monocytes. In conclusion, phosphorus-containing dendrimers appear as precisely tunable nanobiotools able to target and activate human innate immunity and thus prove to be good candidates to develop new drugs for immunotherapies.--Poupot, M., Griffe, L., Marchand, P., Maraval, A., Rolland, O., Martinet, L., L'Faqihi-Olive, F.-E., Turrin, C.-O., Caminade, A.-M., Fournié, J.-J., Majoral, J.-P., Poupot, R. Design of phosphorylated dendritic architectures to promote human monocyte activation.
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.06-5742com