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Front Immunol. 2018 Feb 12;9:131. doi: 10.3389/fimmu.2018.00131. eCollection 2018.

Human Properdin Opsonizes Nanoparticles and Triggers a Potent Pro-inflammatory Response by Macrophages without Involving Complement Activation.

Author information

1
Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United Kingdom.
2
Faculty of Science, Engineering and Computing, Kingston University, Kingston upon Thames, Surrey, United Kingdom.
3
Department of Infection and Immunity, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
4
Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
5
Université de Toulouse, CNRS, INPT, UPS, UMR CNRS-UPS-INP N°5085, 3 Paul Sabatier, Bât. CIRIMAT, Toulouse, France.
6
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

Abstract

Development of nanoparticles as tissue-specific drug delivery platforms can be considerably 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.

KEYWORDS:

carbon nanotubes; complement; cytokines; inflammation; phagocytosis; properdin; thrombospondin repeats

PMID:
29483907
PMCID:
PMC5816341
DOI:
10.3389/fimmu.2018.00131
[Indexed for MEDLINE]
Free PMC Article

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