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Design of phosphorylated dendritic architectures to promote human monocyte activation
Author(s) -
Poupot Mary,
Griffe Laurent,
Marchand Patrice,
Maraval Alexandrine,
Rolland Olivier,
Martinet Ludovic,
L'FaqihiOlive FatimaEzzahra,
Turrin CédricOlivier,
Caminade AnneMarie,
Fournié JeanJacques,
Majoral JeanPierre,
Poupot Rémy
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-5742com
Subject(s) - dendrimer , innate immune system , monocyte , internalization , chemistry , förster resonance energy transfer , microbiology and biotechnology , population , dendritic cell , receptor , fluorescence , immune system , biology , biochemistry , immunology , medicine , physics , environmental health , quantum mechanics
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. FASEB J. 20, 2339–2351 (2006)