Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1

  • Sci Rep. 2017 Nov 30;7(1):16628. doi: 10.1038/s41598-017-16778-4.
Hsin-Hsin Peng  1  2  3  4 ,  Yu-Ju Liu  1  2 ,  David M Ojcius  2  5  6 ,  Chiou-Mei Lee  4 ,  Ren-Hao Chen  7 ,  Pei-Rong Huang  1  2  8 ,  Jan Martel  1  2  5 ,  John D Young  9  10  11  12  13
Affiliations
  • 1. Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan.
  • 2. Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan.
  • 3. Department of Anesthesiology, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan.
  • 4. Laboratory Animal Center, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan.
  • 5. Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan.
  • 6. Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA, 94103, USA.
  • 7. Department of Medical Research and Development, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan.
  • 8. Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan.
  • 9. Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. [email protected].
  • 10. Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. [email protected].
  • 11. Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. [email protected].
  • 12. Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY, 10021, USA. [email protected].
  • 13. Biochemical Engineering Research Center, Ming Chi University of Technology, Taishan, New Taipei City 24301, Taiwan. [email protected].
PMID: 29192209 DOI: 10.1038/s41598-017-16778-4
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.

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