PMID- 29192209 OWN - NLM STAT- MEDLINE DCOM- 20190710 LR - 20190710 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Nov 30 TI - Mineral particles stimulate innate immunity through neutrophil extracellular traps containing HMGB1. PG - 16628 LID - 10.1038/s41598-017-16778-4 [doi] LID - 16628 AB - 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-1beta 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-alpha 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-alpha 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. FAU - Peng, Hsin-Hsin AU - Peng HH AD - Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Department of Anesthesiology, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. AD - Laboratory Animal Center, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. FAU - Liu, Yu-Ju AU - Liu YJ AD - Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. FAU - Ojcius, David M AU - Ojcius DM AD - Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. AD - Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA, 94103, USA. FAU - Lee, Chiou-Mei AU - Lee CM AD - Laboratory Animal Center, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. FAU - Chen, Ren-Hao AU - Chen RH AD - Department of Medical Research and Development, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. FAU - Huang, Pei-Rong AU - Huang PR AD - Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. FAU - Martel, Jan AU - Martel J AD - Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. AD - Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. FAU - Young, John D AU - Young JD AD - Laboratory of Nanomaterials, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. jdyoung@mail.cgu.edu.tw. AD - Center for Molecular and Clinical Immunology, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan. jdyoung@mail.cgu.edu.tw. AD - Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan. jdyoung@mail.cgu.edu.tw. AD - Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY, 10021, USA. jdyoung@mail.cgu.edu.tw. AD - Biochemical Engineering Research Center, Ming Chi University of Technology, Taishan, New Taipei City 24301, Taiwan. jdyoung@mail.cgu.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20171130 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (HMGB1 Protein) RN - 0 (Minerals) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Reactive Oxygen Species) RN - 0 (Toll-Like Receptor 2) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Cell Line MH - Extracellular Traps/*immunology MH - Female MH - HMGB1 Protein/genetics/*metabolism MH - Humans MH - *Immunity, Innate MH - *Immunomodulation MH - Macrophage Activation MH - Macrophages/immunology/metabolism MH - Male MH - Mice MH - Minerals/*immunology MH - Models, Molecular MH - Myeloid Differentiation Factor 88/metabolism MH - Neutrophils/*immunology/*metabolism MH - Reactive Oxygen Species MH - Signal Transduction MH - Toll-Like Receptor 2/metabolism MH - Toll-Like Receptor 4/metabolism MH - Tumor Necrosis Factor-alpha/biosynthesis PMC - PMC5709501 COIS- The authors declare that they have no competing interests. EDAT- 2017/12/02 06:00 MHDA- 2019/07/11 06:00 PMCR- 2017/11/30 CRDT- 2017/12/02 06:00 PHST- 2017/10/02 00:00 [received] PHST- 2017/11/16 00:00 [accepted] PHST- 2017/12/02 06:00 [entrez] PHST- 2017/12/02 06:00 [pubmed] PHST- 2019/07/11 06:00 [medline] PHST- 2017/11/30 00:00 [pmc-release] AID - 10.1038/s41598-017-16778-4 [pii] AID - 16778 [pii] AID - 10.1038/s41598-017-16778-4 [doi] PST - epublish SO - Sci Rep. 2017 Nov 30;7(1):16628. doi: 10.1038/s41598-017-16778-4.