Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1.
ORCiD
David M. Ojcius: 0000-0003-1461-4495
Department
Biomedical Sciences
Document Type
Article
Publication Title
Scientific Reports
ISSN
2045-2322
Volume
7
Issue
1
DOI
10.1038/s41598-017-16778-4
First Page
1
Last Page
16
Publication Date
11-30-2017
Abstract
Calcium phosphate-based mineralo-organic particles form spontaneously in the body and may represent precursors of ectopic calcification. We have shown earlier that these particles induce activation of caspase-1 and secretion of IL-1β by macrophages. However, whether the particles may produce other effects on immune cells is unclear. Here, we show that these particles induce the release of neutrophil extracellular traps (NETs) in a size-dependent manner by human neutrophils. Intracellular production of reactive oxygen species is required for particle-induced NET release by neutrophils. NETs contain the high-mobility group protein B1 (HMGB1), a DNA-binding protein capable of inducing secretion of TNF-α by a monocyte/macrophage cell line and primary macrophages. HMGB1 functions as a ligand of Toll-like receptors 2 and 4 on macrophages, leading to activation of the MyD88 pathway and TNF-α production. Furthermore, HMGB1 is critical to activate the particle-induced pro-inflammatory cascade in the peritoneum of mice. These results indicate that mineral particles promote pro-inflammatory responses by engaging neutrophils and macrophages via signaling of danger signals through NETs.
Recommended Citation
Peng, H.,
Liu, Y.,
Ojcius, D. M.,
Lee, C.,
Chen, R.,
Huang, P.,
Martel, J.,
&
Young, J. D.
(2017).
Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1..
Scientific Reports, 7(1), 1–16.
DOI: 10.1038/s41598-017-16778-4
https://scholarlycommons.pacific.edu/dugoni-facarticles/438
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
