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Human properdin opsonizes nanoparticles and triggers a potent pro-inflammatory response by macrophages without involving complement activation

Kouser, Lubna and Paudyal, Basudev and Kaur, Anuvinder and Stenbeck, Gudrun and Jones, Lucy A. and Abozaid, Suhair M. and Stover, Cordula M. and Flahaut, Emmanuel and Sim, Robert B. and Kishore, Uday Human properdin opsonizes nanoparticles and triggers a potent pro-inflammatory response by macrophages without involving complement activation. (2018) Frontiers in Immunology, 9. 1-18. ISSN 1664-3224

(Document in English)

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Official URL: http://dx.doi.org/10.3389/fimmu.2018.00131


Development of nanoparticles as tissue-specific drug delivery platforms can be consid erably influenced by the complement system because of their inherent pro-inflammatory and tumorigenic consequences. The complement activation pathways, and its recognition subcomponents, can modulate clearance of the nanoparticles and subsequent inflammatory response and thus alter the intended translational applications. Here, we report, for the first time, that human properdin, an upregulator of the complement alternative pathway, can opsonize functionalized carbon nanotubes (CNTs) via its thrombospondin type I repeat (TSR) 4 and 5. Binding of properdin and TSR4+5 is likely to involve charge pattern/ polarity recognition of the CNT surface since both carboxymethyl cellulose-coated carbon nanotubes (CMC-CNT) and oxidized (Ox-CNT) bound these proteins well. Properdin enhanced the uptake of CMC-CNTs by a macrophage cell line, THP-1, mounting a robust pro-inflammatory immune response, as revealed by qRT-PCR, multiplex cytokine array, and NF-κB nuclear translocation analyses. Properdin can be locally synthesized by immune cells in an inflammatory microenvironment, and thus, its interaction with nanoparticles is of considerable importance. In addition, recombinant TSR4+5 coated on the CMC-CNTs inhibited complement consumption by CMC-CNTs, suggesting that nanoparticle decoration with TSR4+5, can be potentially used as a complement inhibitor in a number of pathological contexts arising due to exaggerated complement activation.

Item Type:Article
Additional Information:Thanks to Frontiers Media editor. The original PDF of the article can be found at https://www.frontiersin.org/articles/10.3389/fimmu.2018.00131/full
HAL Id:hal-01728830
Audience (journal):International peer-reviewed journal
Uncontrolled Keywords:
Institution:French research institutions > Centre National de la Recherche Scientifique - CNRS (FRANCE)
Université de Toulouse > Institut National Polytechnique de Toulouse - Toulouse INP (FRANCE)
Other partners > Kingston University (UNITED KINGDOM)
Université de Toulouse > Université Toulouse III - Paul Sabatier - UT3 (FRANCE)
Other partners > University of Leicester (UNITED KINGDOM)
Other partners > Brunel University (UNITED KINGDOM)
Other partners > King Faisal Specialist Hospital and Research Centre - KFSH&RC (SAUDI ARABIA)
Other partners > University of Oxford (UNITED KINGDOM)
Laboratory name:
Deposited On:12 Mar 2018 09:02

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