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

Frontiers in Immunology
Lubna KouserUday Kishore

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 additi...Continue Reading

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Citations

Sep 5, 2019·Journal of Clinical Medicine·Na-Ra HanHyun-Ja Jeong
Sep 12, 2019·Frontiers in Immunology·Dennis V PedersenGregers R Andersen
Oct 21, 2020·Microorganisms·Nikola PopovićAmarela Terzić-Vidojević
Jan 26, 2021·Frontiers in Immunology·Ninh M La-BeckMaciej M Markiewski
Feb 6, 2021·Frontiers in Immunology·Alessandro MangognaUday Kishore
Dec 11, 2020·Environmental Pollution·Felipe Gomes PinheiroWalter Araujo Zin
Nov 7, 2020·Frontiers in Immunology·Emanuele PapiniFabrizio Mancin

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Methods Mentioned

BETA
PCR
PMA
transfection
ELISA
Fluorescence
fluorescence microscopy
nuclear translocation

Software Mentioned

LAS
GraphPad
Step One
Gatan microscopy
GraphPad Prism

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