Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):E5856-E5865. Epub 2016 Sep 19.

Nanoparticles size-dependently initiate self-limiting NETosis-driven inflammation.

Author information

1
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
2
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine.
3
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan Province, China.
4
Electron Devices, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91058, Germany.
5
Section for Experimental Oncology and Nanomedicine, Department of Otorhinolaryngology, Head, and Neck Surgery, University Hospital Erlangen, 91054 Erlangen, Germany.
6
Division of Molecular Immunology, Department of Internal Medicine 3, Nikolaus Fiebiger Center, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
7
Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine.
8
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 610041 Chengdu, Sichuan Province, China; zhao.y1977@163.com martin.herrmann@uk-erlangen.de.
9
Department of Internal Medicine 3-Rheumatology and Immunology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Germany; zhao.y1977@163.com martin.herrmann@uk-erlangen.de.

Abstract

The critical size for strong interaction of hydrophobic particles with phospholipid bilayers has been predicted to be 10 nm. Because of the wide spreading of nonpolar nanoparticles (NPs) in the environment, we aimed to reveal the ability of living organisms to entrap NPs via formation of neutrophil extracellular traps (NETs). Upon interaction with various cell types and tissues, 10- to 40-nm-sized NPs induce fast (<20 min) damage of plasma membranes and instability of the lysosomal compartment, leading to the immediate formation of NETs. In contrast, particles sized 100-1,000 nm behaved rather inertly. Resulting NET formation (NETosis) was accompanied by an inflammatory reaction intrinsically endowed with its own resolution, demonstrated in lungs and air pouches of mice. Persistence of small NPs in joints caused unremitting arthritis and bone remodeling. Small NPs coinjected with antigen exerted adjuvant-like activity. This report demonstrates a cellular mechanism that explains how small NPs activate the NETosis pathway and drive their entrapping and resolution of the initial inflammatory response.

KEYWORDS:

NETosis; inflammation; nanoparticles; neutrophils; size

PMID:
27647892
PMCID:
PMC5056044
DOI:
10.1073/pnas.1602230113
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center