PMID- 35936002 OWN - NLM STAT- MEDLINE DCOM- 20220809 LR - 20220817 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Nano-silica particles synergistically IgE-mediated mast cell activation exacerbating allergic inflammation in mice. PG - 911300 LID - 10.3389/fimmu.2022.911300 [doi] LID - 911300 AB - BACKGROUND: Allergic respiratory diseases have increased dramatically due to air pollution over the past few decades. However, studies are limited on the effects of inorganic components and particulate matter with different particle sizes in smog on allergic diseases, and the possible molecular mechanism of inducing allergies has not been thoroughly studied. METHODS: Four common mineral elements with different particle sizes in smog particles were selected, including Al(2)O(3), TiO(2), Fe(2)O(3), and SiO(2). We studied the relationship and molecular mechanism of smog particle composition, particle size, and allergic reactions using mast cells, immunoglobulin E (IgE)-mediated passive cutaneous anaphylaxis (PCA) model, and an ovalbumin (OVA)-induced asthmatic mouse model in vitro and in vivo, combined with transmission electron microscopy, scanning transmission X-ray microscopy analysis, and transcriptome sequencing. RESULTS: Only 20 nm SiO(2) particles significantly increased beta-hexosaminidase release, based on dinitrophenol (DNP)-human serum albumin (HSA) stimulation, from IgE-sensitized mast cells, while other particles did not. Meanwhile, the PCA model showed that Evan's blue extravasation in mice was increased after treatment with nano-SiO(2) particles. Nano-SiO(2) particles exposure in the asthmatic mouse model caused an enhancement of allergic airway inflammation as manifested by OVA-specific serum IgE, airway hyperresponsiveness, lung inflammation injury, mucous cell metaplasia, cytokine expression, mast cell activation, and histamine secretion, which were significantly increased. Nano-SiO(2) particles exposure did not affect the expression of FcϵRI or the ability of mast cells to bind IgE but synergistically activated mast cells by enhancing the mitogen-activated protein kinase (MAPK) signaling pathway, especially the phosphorylation levels of the extracellular signal-regulated kinase (ERK)1/2. The ERK inhibitors showed a significant inhibitory effect in reducing beta-hexosaminidase release. CONCLUSION: Our results indicated that nano-SiO(2) particles stimulation might synergistically activate IgE-sensitized mast cells by enhancing the MAPK signaling pathway and that nano-SiO(2) particles exposure could exacerbate allergic inflammation. Our experimental results provide useful information for preventing and treating allergic diseases. CI - Copyright (c) 2022 Yang, Cao, Wang, Liu, Zhu, Zou, Ma, Luo, Shao, Xu, Wei and Sun. FAU - Yang, Yong-Shi AU - Yang YS AD - Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. FAU - Cao, Meng-Da AU - Cao MD AD - Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Wang, An AU - Wang A AD - Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China. FAU - Liu, Qing-Mei AU - Liu QM AD - Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. FAU - Zhu, Dan-Xuan AU - Zhu DX AD - Women and Children Central Laboratory, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. FAU - Zou, Ying AU - Zou Y AD - Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, China. AD - Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China. FAU - Ma, Ling-Ling AU - Ma LL AD - Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China. FAU - Luo, Min AU - Luo M AD - Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China. FAU - Shao, Yang AU - Shao Y AD - Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China. FAU - Xu, Dian-Dou AU - Xu DD AD - Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, China. FAU - Wei, Ji-Fu AU - Wei JF AD - Research Division of Clinical Pharmacology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China. AD - Department of Pharmacy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China. FAU - Sun, Jin-Lyu AU - Sun JL AD - Department of Allergy, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220722 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Smog) RN - 37341-29-0 (Immunoglobulin E) RN - 7631-86-9 (Silicon Dioxide) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 3.2.1.52 (beta-N-Acetylhexosaminidases) SB - IM MH - Animals MH - *Asthma MH - Disease Models, Animal MH - Humans MH - *Hypersensitivity MH - Immunoglobulin E MH - Inflammation MH - *Lung Injury MH - Mast Cells MH - Mice MH - Mitogen-Activated Protein Kinases MH - Silicon Dioxide/adverse effects MH - Smog MH - beta-N-Acetylhexosaminidases PMC - PMC9355306 OTO - NOTNLM OT - MAPK OT - allergic asthma OT - mast cell OT - silica nanoparticles OT - smog particles COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/08/09 06:00 MHDA- 2022/08/10 06:00 PMCR- 2022/01/01 CRDT- 2022/08/08 03:42 PHST- 2022/04/02 00:00 [received] PHST- 2022/06/27 00:00 [accepted] PHST- 2022/08/08 03:42 [entrez] PHST- 2022/08/09 06:00 [pubmed] PHST- 2022/08/10 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.911300 [doi] PST - epublish SO - Front Immunol. 2022 Jul 22;13:911300. doi: 10.3389/fimmu.2022.911300. eCollection 2022.