Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 40, Pages E5856-E5865Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1602230113
Keywords
nanoparticles; size; neutrophils; NETosis; inflammation
Categories
Funding
- National Science Foundation of China [81273286]
- International Collaborative Project in Science and Technology of Sichuan Province [2015HH0050]
- German Research Council (GRC) [CRC-643-B5, CRC-643-B8, CRC-1181-C03, KFO257]
- Osteoimmunology IMMUNOBONE [SPP 1468]
- doctoral training programs [GK1660, SFB643]
- Innovative Medicines Initiative-research project Be The Cure (BTCure)
- Interdisciplinary Center for Clinical Research of the University of Erlangen-Nuremberg [IZKF-J41]
- Pathogen and Graphene (PANG) (H-MSCE-RISE) [690836]
- National Academy of Sciences of Ukraine
- Bavarian State Ministry for the Environment and Consumer Protection
- GRC through the Cluster of Excellence Engineering of Advanced Materials
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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 cellularmechanism that explains how small NPs activate the NETosis pathway and drive their entrapping and resolution of the initial inflammatory response.
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