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An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice

Visnovitzné Dr Vukman, Krisztina and Ferencz, Andrea and Fehér, Daniella and Juhos, Krisztina and Lőrincz, Péter and Visnovitz, Tamás and Koncz, Anna and Pálóczi, Krisztina and Försönits, András and Khamari, Delaram and Galinsoga, Alicia and Drahos, László and Buzás, Edit Irén (2020) An implanted device enables in vivo monitoring of extracellular vesicle-mediated spread of pro-inflammatory mast cell response in mice. JOURNAL OF EXTRACELLULAR VESICLES, 10 (1). ISSN 2001-3078

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Abstract

Abstract Mast cells have been shown to release extracellular vesicles (EVs) in vitro. However, EV-mediated mast cell communication in vivo remains unexplored. Primary mast cells from GFP-transgenic and wild type mice, were grown in the presence or absence of lipopolysaccharide (LPS), and the secreted EVs were separated from the conditioned media. Mast cell-derived EVs were next cultured with LPS-naïve mast cells, and the induction of TNF-α expression was monitored. In addition, primary mast cells were seeded in diffusion chambers that were implanted into the peritoneal cavities of mice. Diffusion chambers enabled the release of GFP+ mast cell-derived EVs in vivo into the peritoneal cavity. Peritoneal lavage cells were assessed for the uptake of GFP+ EVs and for TNF-α production. In vitro, LPS-stimulated mast cell-derived EVs were efficiently taken up by non-stimulated mast cells, and induced TNF-α expression in a TLR4, JNK and P38 MAPK dependent manner. In vivo, using implanted diffusion chambers, we confirmed the release and transmission of mast cell-derived EVs to other mast cells with subsequent induction of TNF-α expression. These data show an EV-mediated spreading of pro-inflammatory response between mast cells, and provide the first in vivo evidence for the biological role of mast cell-derived EVs.

Item Type: Article
Additional Information: Funding Agency and Grant Number: Hungarian ScientificResearch FundOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [OTKA11958, OTKA120237, PD112085]; NVKP [NVKP_16-1-20160017]; VEKOP [VEKOP2.3.2-16-2016-00002, VEKOP-2.3.3-15-2016-00016]; Higher Education Excellence Program, Hungary; Horizon 2020 Framework Programme [739593]; [H2020-MSCA-ITN-2017722148TRAINEV] Funding text: Hungarian ScientificResearch Fund, Grant/Award Numbers: OTKA11958, OTKA120237, PD112085; NVKP, Grant/AwardNumber: NVKP_16-1-20160017; VEKOP, Grant/AwardNumbers: VEKOP2.3.2-16-2016-00002, VEKOP-2.3.3-15-2016-00016; Higher Education Excellence Program, Hungary; Directorate-General forResearch and Innovation, Grant/AwardNumber: H2020-MSCA-ITN-2017722148TRAINEV; Horizon 2020 Framework Programme, Grant/AwardNumber: 739593 Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary Department of Surgical Research and Techniques, Semmelweis University, Budapest, Hungary Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest, Hungary MS Proteomics Research Group, Hungarian Academy of Sciences, Institute of Organic Chemistry, Budapest, Hungary MTA-SE Immune-Proteogenomics Extracellular Vesicle Research Group, Budapest, Hungary HCEMM-SE Extracellular Vesicle Research Group, Budapest, Hungary Export Date: 29 March 2021 Correspondence Address: Vukman, K.V.; Department of Genetics, Hungary; email: vukman.krisztina@med.semmelweis-univ.hu
Uncontrolled Keywords: In Vitro; mast cell; In vivo; TNF-α; LPS; Extracellular vesicles;
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH426 Genetics / genetika, örökléstan
R Medicine / orvostudomány > R1 Medicine (General) / orvostudomány általában
SWORD Depositor: MTMT SWORD
Depositing User: MTMT SWORD
Date Deposited: 06 Apr 2021 11:45
Last Modified: 06 Apr 2021 11:45
URI: http://real.mtak.hu/id/eprint/123428

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