Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/LCMSsamplelist.xlsxftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/2678_cells_Fusion_170814_14_33.msfftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_28.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_15.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_26.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_17.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_22.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_33.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_20.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_19.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_25.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_31.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_14.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_27.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_29.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_23.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_16.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_32.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_21.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_30.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_18.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD048039/Fusion_170814_24.rawprimaryOK200praveen.papareddy@med.lu.seProteomics Core FacilityMass SpectrometryBottom-up proteomicsStxbp1ReceptorsExtracellular vesiclesTnfr1Il1r1 and phosphorylationExosomesFusionhttps://www.ebi.ac.uk/pride/archive/projects/PXD048039Blood PlasmaPreparation of large EVs from human plasma or from cell supernatants. Human plasma samples were prepared by centrifuging blood at 1,000 x g for 10 min. Samples were frozen (−80°C) until use. After thawing at 37°C remaining cells were removed by centrifugation at 300 x g for 10 min. The collected supernatants were subjected to another centrifugation step at 5,000 x g for 10 min in order to remove apoptotic bodies and cell debris. EVs were then extracted from the plasma and cell supernatants by a third centrifugation step at 21,000 x g for 30 min at 20 °C. Control EVs were isolated from citrate plasma from a group of healthy people. Protein Digestion and Tandem Mass Tag (TMT) Labeling Ten μg of each of 8 samples, 3.4 µg from a control sample and a reference pool made from 5 mg from 4 samples (totally 20 µg) were lysed by shaking in in 2% sodium dodecyl sulfate (SDS) in 50 mM triethylammonium bicarbonate (TEAB). The samples were digested with trypsin using the filter-aided sample preparation (FASP) method 47. Briefly, the samples were reduced with 100 mM dithiothreitol at 60°C for 30 min. The reduced samples were transferred to 30 kDa MWCO Pall Nanosep centrifugation filters (Pall Corporation), washed several times with 8 M urea and once with digestion buffer (DB, 0.5% sodium deoxycholate in 50 mM TEAB) prior to alkylation with 10 mM methyl methanethiosulfonate in digestion buffer for 20 min in room temperature. Digestions were performed by addition of Pierce MS grade Trypsin (Thermo Fisher Scientific) in DB to a trypsin:protein ratio of 1:100 and incubated overnight at 37°C. Next morning an additional portion of trypsin was added and incubated for another three hours. Peptides were collected by centrifugation and labelled using TMT 10-plex isobaric mass tagging reagents (Thermo Scientific) according to the manufacturer’s instructions. Labelled samples from each sample type were combined into 2 sets and sodium deoxycholate was removed by acidification with 10% TFA. The combined TMT-labeled samples were desalted using Pierce Peptide Desalting Spin Columns (Thermo Scientific) following the manufacturer’s instructions. Fractionation and nLC-MS/MS Analysis Each set was pre-fractionated on the Dionex Ultimate 3000 UPLC system (Thermo Fischer Scientific) using the Waters XBridge BEH C18 column (3.0 x 150 mm, 3.5µm, Waters Corporation, Milford, USA) and the gradient from 3% to 40% solvent B over 18 min, from 40% to 100% B over 5 min, 100% B for 5 min, all at the flowrate of 0.4 ml/min; solvent A was 10 mM ammonium formate in water at pH 10.0, solvent B was 90% acetonitrile, 10% 10 mM ammonium formate in water at pH 10.0. The 40 primary fractions were concatenated into 20 fractions, evaporated and reconstituted in 3% acetonitrile, 0.2% formic acid for nLC-MS/MS analysis. Each fraction was analyzed on Orbitrap Fusion Tribrid mass spectrometer interfaced with Easy-nLC 1200 nanoflow liquid chromatography system (Thermo Fisher Scientific). Peptides were trapped on the Acclaim Pepmap 100 C18 trap column (100 μm x 2 cm, particle size 5 μm, Thermo Fischer Scientific) and separated on the in-house packed C18 analytical column (75 μm x 32 cm, particle size 3 μm) using the gradient from 5% to 32% B in 75 min, from 32% to 100% B in 5 min, and 100% B for 10 min at a flow of 300 nl/min. Solvent A was 0.2% formic acid and solvent B was 80% acetonitrile, 0.2% formic acid. MS scans were performed at 120,000 resolution, m/z range 380-1200. MS/MS analysis was performed in a data-dependent mode, with top speed cycle of 3 s for the most intense doubly or multiply charged precursor ions. Precursor ions were isolated in the quadrupole with a 0.7 m/z isolation window, with dynamic exclusion set to 10 ppm and duration of 45 s. Isolated precursor ions were subjected to collision induced dissociation (CID) at 35 collision energy with a maximum injection time of 50 ms. Produced MS2 fragment ions were detected in the ion trap followed by multinotch (simultaneous) isolation of the top 7 most abundant fragment ions for further fragmentation (MS3) by higher-energy collision dissociation (HCD) at 60% and detection in the Orbitrap at 50,000 resolutions, m/z range 100-500.PrideNot availableDatabase Search and Quantification MS raw data files for the TMT set were merged for relative quantification and identification using Proteome Discoverer version 1.4 (Thermo Fisher Scientific). A database search for each set was performed with the Mascot search engine (Matrix Science) using the Homo Sapiens Swissprot database, version Mars 2017 with 553941sequences. MS peptide tolerance of 5 ppm and MS/MS tolerance for identification of 600 millimass units (mmu), tryptic peptides with zero missed cleavage and variable modifications of methionine oxidation, fixed modifications of cysteine alkylation, N-terminal TMT-label and lysine TMT-label were selected. The detected peptide threshold in the software was set to a significance of FDR 1% by searching against a reversed database and identified proteins were grouped by sharing the same sequences to minimize redundancy. For TMT quantification, the ratios of the TMT reporter ion intensities in HCD MS/MS spectra (m/z 126-131) from raw data sets were used. Ratios were derived by Proteome Discoverer using the following criteria: fragment ion tolerance as 3 mmu for the centroid peak with smallest delta mass and minimum intensity of 2,000. Only peptides unique for a given protein were considered for relative quantitation, excluding those common to other isoforms or proteins of the same family. The quantification was normalized using the protein median. Calculations of the ratios were made by using a reference sample made from a mix of 4 of the samples or the control sample as denominator.ProteomicsPraveen PapareddyDivision of Infection Medicine, Department of Clinical Sciences, Lund, Lund University, Biomedical Center, Tornavägen 10, SE-22184 Lund, SwedenPARTIALHomo Sapiens (human)gupcf@outlook.com38326335 Papareddy P, Tapken I, Kroh K, Varma Bhongir RK, Rahman M, Baumgarten M, Cim EI, Györffy L, Smeds E, Neumann A, Veerla S, Olinder J, Thorlacus H, Ryden C, Bartakova E, Holub M, Herwald H. The role of extracellular vesicle fusion with target cells in triggering systemic inflammation. Nat Commun. 2024 15(1):1150 10.1038/s41467-024-45125-1SAMBIO Core Facilities, Sahgrenska Academy, University of GothenburgSwedenExtracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.The role of extracellular vesicle fusion with target cells in triggering systemic inflammation.Papareddy Praveen P, Tapken Ines I, Kroh Keshia K, Varma Bhongir Ravi Kiran RK, Rahman Milladur M, Baumgarten Maria M, Cim Eda Irem EI, Györffy Lilla L, Smeds Emanuel E, Neumann Ariane A, Veerla Srinivas S, Olinder Jon J, Thorlacus Henrik H, Ryden Cecilia C, Bartakova Eva E, Holub Michal M, Herwald Heiko HInflammatory Response, Innate Inflammatory Responses., Exovesicles, inflammatory response, Inflammations, Apoptotic Body, Bodies, Apoptotic Bodies, Vesicles, inflammation, Extracellular Vesicle, Body, Cell, microparticle, Concept, Vesicle, Role Concept, Innate Inflammatory Response, Roles, Extracellular, Role Concepts, Apoptotic, Role, Concepts, Innate, ExovesicleWater, sodium salt, l(4)17, CPD photolyase activity, l(4)13, ammonium formate, Gli, 13C-labeled, Size, MeCN, cadmium salt, Scx, PhrB photolyase activity, ion, TFA, Cid[Mel], fond, Ci[D], Particle, H(2)O, A4, BOUND WATER, SDH, Basodexan, magnesium formate, CycEI, oxidane, Deoxycholic Acid, zinc salt, heavy chain disease, Solvent, CENP-A, prevention, Long Term, thomson., WATER, CENP-C, l(2)k09905, HOH, 5730420M11Rik, dmTAF[[II]]230, SDS, Polypeptides, DmelCG11081, cobalt(II) formate dihydrate, Method, GRP1, DPlexA, CH3-C#N, Grp1, B1, 1, 2, 3, NUP96, myd, epithelium, MMTS, WMS, (R*, Disodium Salt, DmelCG8428, Fresh Frozen, SET, Spin, BcDNA:RE21270, TFIID TAF250, cel, PTPSTEP, Mbp-1, CG17245, SUPPRESSOR OF AUXIN RESISTANCE 3, AI047805, DmelCG4299, citrate, set, SPIN, CI, column, BTKAP1, sample, D1, 3beta-Isomer, methyl methanesulfonothioate, GTFII-I, plasma, Magnesium (2:1) Salt, GPH, SGS, nickel salt, CiD, 6030441I21Rik, Ce, dTAF[[II]]230, preventive therapy, Degradations, Ci, Citrate, cobalt (+2) salt, Liquid Chromatography, TAF200, Longterm Effect, Procedure, BAP135, Cyc E, collisionally activated dissociation, CG3428, Cid, CID, ciD, ACMICD, CITRATE ANION, TPSG1, H2O, Dihydroxycholanoic Acid, sodium (4:1:1) salt, BG:DS07108.3, Dm1, magnesium salt, mKIAA0609, dipyrimidine photolyase (photosensitive), Sizes, ci-D, BAP-135, l(2)05206, BcDNA:GM05237, 5beta, Hydrogen Oxide, fg, portion of blood plasma, HLA-DR-associated protein II, DI-2, CENP-A/Cid, CENP-A/CID, CG11628, CENPA, Anhydrous Citric Acid, I-2Dm, cit, Protein Digestions, formate, expanded, Shwachman-Diamond type metaphyseal dysplasia, methyl methanethiolsulfonate, reagent, cromium (+3), Striatum-enriched protein-tyrosine phosphatase, Shwachman syndrome, Methodological, GtfII-I, beta Trypsin, human, I-2PP1, 12beta-Isomer Deoxycholic Acid, Speed, MDC1D, blood plasm, Sodium Salt, 5alpha-Isomer, l(2)W5, TAF-IBETA, enr, Taf250, PRSS31, Indicator, ammonium (4:1) salt, TAF-Ibeta, methyl cyanide, lead (+2) salt, TMT, 4-Dimercapto-2, Ci-155, TAF230, big, Fresh, Cleland Reagent, 5alpha Isomer, F10B6_15, Particle Sizes, rac-Dithiothreitol, GRP1/cytohesin 1, nickel formate dihydrate, cycline, Fresh Frozen Plasma, lead formate, Effects, threo-1, Cleland's reagent, DmcyclinE, Sodium Lauryl, aluminum salt, Pierce, 4-dimercapto-, Carbamide, Antp P1, precursor, Antp P2, R*)-, thomson, Chalk, body system, CG7826, F10B6.15, deoxyribodipyrimidine photolyase activity, agua, Human, mass-to-charge ratio, CG11633, cdi7, CenpA, large, cyclinE, 12-dihydroxy-, IT, Hu, CG7835, Cdi7, CDI7, CG42273, system, Carmol, 12alpha)-, MAM, 3.4, Siah, Man, Technique, portion of blood, 12beta Isomer, anatomical systems, dTAF[[II]]250, thallium (+1) salt, Longterm, cell, MDDGB6, plex A, beta-Trypsin, Monosodium Salt, plex B, rubidium salt, 3beta Isomer, F23A5.3, 4733401P19Rik, 2pp2a, Long-Term, methanoic acid, DmcycE, ions, man, CG1028, CG10574, CD156, DmelCG17245, Study, Injectable, dTAF250, 2PP2A, congenital lipomatosis of pancreas, dSET, dSet, 3-propanetricarboxylate, Kybella, CG2125, peptidos, Choleic Acid, Anhydrous, PTHB1, 3-butanediol, WBSCR6, Sulfuric acid monododecyl ester sodium salt, grupo, whole blood, 1-(14)C-labeled, 5alpha-Isomer Deoxycholic Acid, Clelands Reagent, stepk, BG:DS00004.13, potassium formate, copper (+2) salt, DmAntp, acetonitrile, buffer, Digestions, Cell, Dithiothreitol, bnch, dTAF230, CD142, Frozen Plasmas, polypeptide, l(2)k02511, Sodium Lauryl Sulfate, l(2)k02514, Temperatures, DmCycE, Proteolyses, carbonyldiamide, I-2PP2A, ci[D], C18, cupric formate, chemical analysis, Dm I-2, Long Term Effects, 3beta-Isomer Deoxycholic Acid, TAF[[II]]250/230, MFS1, Sodium, aluminum formate, DTL, Cleland's, Taf[[II]]250, AU020952, covalent modifier, DTT, Ant, RPE, lithium formate, l(2)k02602, DmelCG2125, CenH3, ci155, DMDA1, ensemble, underdeveloped, prophylaxis, SWDS, Shwachman-Bodian-Diamond syndrome, Monopotassium Salt, ethanenitrile, CD156a, 3-propanetricarboxylic acid, DmelCG11628, Longterm Effects, ME-IV, p. pigmentosa retinae, plan specification, Cleland's Reagent, D-CycE, Ns, DmelCG1028, control, Pancreatic insufficiency and bone marrow dysfunction, DRO15DC96Z, deoxyribonucleate pyrimidine dimer lyase (photosensitive), [OH2], CenpA/CID, Sulfate, DIWS, IPP2A2, ANT-C, Sodium Dodecyl, Meth, NCMe, determination, Blood, Antp1, Dodecyl Sulfate, Mbp1, zinc formate, lead salt, ion(3-), pigmented epithelium, Alkylations, 12beta-Isomer, peptide, Techniques, ammonium tetraformate, FBXO1, peptido, Ccne, DmelCG3428, congenital, AntP1, Min, Williams-Beuren syndrome chromosomal region 6 protein, prevention and control, Injectables, Effect, DmelCG42273, CG13329, Fresh Frozen Plasmas, Man (Taxonomy), reference sample, kDa, peptides, TAF-I, E927b, E430039A18Rik, hypoplasia, pigmented retina, min, mAPC, Lauryl Sulfate, copper, Protein Degradation, DNA cyclobutane dipyrimidine photolyase activity, lipomatosis of pancreas, BG:DS07700.1, preventive measures, IGAAD, lithium salt, Methodological Studies, SOLO DANCERS, Sputolysin, DmelCG10574, Ice, 380, l(2)k08110, Diws1t, ppm, Cenp-A, dihydridooxygen, ANT-P, TF, Shwachman-Bodian syndrome, TEAB, Reagents, dihydrogen oxide, GPHYSD2, ammonium (2:1) salt, Long-Term Effects, reagents, phapii, PRE, Frozen Plasma, gyltl1b-b, Modern, Citric Acid Monohydrate, deoxyribonucleic cyclobutane dipyrimidine photolyase activity, aqua, Dmel_CG7826, AI836084, StF-IT-1, Th, 4-dimercapto-2, 2-hydroxytricarballylate, TAFII-250, TAF250/230, br37, Plasmas, Thermo Scientific, Citric Acid, ur, Aus, carbamide, TAFII250, S-adenosyl-L-methionine:thiol S-methyltransferase activity, HCD, Cleland, retinal pigment, Ionen, Digestion, MDDGA6, 3.1.3.48, SRF-Phox1-interacting protein, KIAA0609, reactif, nickel (+2) salt, PlexA1, retinal pigment layer, Dmel_CG7835, Crystal, cenpA, Mnb, MNB, parent ion, l(2R)W5, ammonium salt, gyltl1b, CenH3/CID, Ci/Gli, Ci/GLI, PlexB, Step, PlexA, acidification, MS/MS, Xylella fastidiosa str. Temecula1, mdc1d, hydrogen hydroxide, cobaltous formate, 3-Butanediol, MASS, CG4299, AW124434, CG17603, TAF[[II]], Methodological Study, Plex1, acqua, organ system, 2-hydroxy-1, Irium, R*)-1, H2NC(O)NH2, phr A photolyase activity, DMDA, DNA-photoreactivating enzyme, l35Dd, 3-propanetricarboxylate(3-), precursor ion, enlarged, WBS, STEP, SR3-5, copper salt, CG8428, Polypeptide, Wasser, PLEXB, i2pp2a, 1728, Gruppe, Cholan-24-oic acid, d230, human being, Procedures, Reagent, Degradation, cesium salt, Lagodeoxycholic Acid, FBN, DMANTPE1, dTAFII250, CG11081, cycE, photoreactivating enzyme activity, EfW1, TYPE, TFII-I, l(2)br37, froggy, cit(3-), PHAPII, Gyltl1a, CYCLE, Buffer, Bruton tyrosine kinase-associated protein 135, formic acid, DAGA4, cytohesin/GRP1, Karbamid, l(4)102ABc, method, potassium salt, Homo sapiens, reduced, dmTAF1, Taf230, ECTOL1, Injection, 14C-labeled, method used in an experiment, Harnstoff, Tina, Studies, Sodium Deoxycholate, IB291, D-Plex A, stratum pigmentosa retinae, tiny, AA673430, SCG3, Reagents and Indicators, TAF250, CenH3[Cid], CenH3[CID], ANTC, Blood Plasma, Taf200, antp, MOS3, deoxyribocyclobutadipyrimidine pyrimidine-lyase activity, Glass, CYCE, reactivo, PRECOCIOUS, MS3, MS2, DmelCG3938, iones, CyclE, ipp2a2, l(2)SH2 0323, 3938, DmelCG13329, Taf1p, LARGE, labeling, Desoxycholic Acid, eau, calcium formate, Protein Degradations, Indicators, OCTD, Xylella fastidiosa (strain Temecula1 / ATCC 700964), l(2)k05007, X-linked combined immunodeficiency, BPFD#36, dm-cycE, Neural-specific protein-tyrosine phosphatase, 10^[-6], grupos, taf-ibeta, great, Blood Plasmas, cromium (+3) salt, Long-Term Effect, AA553322, BTK-associated protein 135, AntP, ANTP, TAF, TAG, F23A5_3, sodium formate, thiol methyltransferase activity, Controlled, small, Monoammonium Salt, DYRK1, Controlling, data, TAF[[II]]250, nickel formate, 3H-labeled, vertebrate blood, igaad, strontium formate, l(3)84Ab, Deoxycholate, cenH3, Protein Digestion, strontium salt, plex, Peptide, group, LGMD2C, Dithiotreitol, MODIFIER OF SNC1, CAD, Ci155, p230, water, Protein, DL-threo-1, I2PP2A, deoxyribonucleic photolyase activity, TFIID, Dyrk1, 25/11, l(3)84Ba, CyeE, connected anatomical system, (3alpha, l(2)SH0323, ACETONITRILE, tandem MS, WMS2, cyanomethane, CYH1, Plasma, Uralyt U, TAF[[II]]230, PRSS, uree, photolyase activity, CC1, l(2)35Dd, Rest, Tripcellim, portion of plasma, TAF[II]250, CGI-97, sample population, chromic formate, l(2)10403, Trypure, dSET/TAF-Ibeta, 2610030F17Rik, DmelCG17603, Ion, Modern Man, SSKS, SCARMD2, calcium salt, Peptid, assay, AA407739, CG3938, groupe, TAF1, CID/CENP-Aprojections, nucleocytoplasm, Inflammations, determination, Laboratory, Mus domesticus, Heparinic acid, CASP-14, Extracellular Vesicle, protein, neutral molecular compounds, House Mouse, dmTAF[[II]]230, heparina, Personal, protein polypeptide chains, heparine, Communications, Roles, Sandoparin, symptoms, Concepts, Donator, Miscommunication, protein aggregate, molecule, molecula, imprinted and ancient gene protein, increased, Heparinic Acid, molecules, inflammatory response, TFIID TAF250, cel, Personnel, Tissue, Swiss Mice, proteins, Social Communications, Molekuel, Communication, Social, Cy 222, Reviparin, papilla, Role Concepts, Tissue Donor, intracellular, single organism signaling, screening, dTAF[[II]]230, Transplant Donor, Unfractionated Heparin, Social Communication, Transplant, lamina, mouse, TAF200, Semen Donors, flanges, TAFII-250, TAF250/230, Programs, Bemiparin, Program, TAFII250, Role Concept, agonist, Apoptotic, Mini-ICE, shelf, Role, Donors, internal to cell, activation, Mus musculus, Caspase-14 subunit p10, mice, shelves, Swiss Mouse, signs, Caspase-14 subunit p19, CG17603, MICE, projection, TAF[[II]], ridge, Semen Donor, domesticus, Semen, Taf250, antagonists and inhibitors, SR3-5, Mouse, Communication Program, Sodium Heparin, E430016J11Rik, Ovum, Ovum Donors, Organ Donors, Innate, TAF230, accessory, Misinformation, 3.4.22.-, Inflammatory Response, d230, Exovesicles, Apoptotic Body, Bodies, lamellae, Vesicles, Gene, dTAFII250, mini-ICE, protein-containing complex, Ximpact, EfW1, process of organ, supernumerary, lamella, Certoparin, Enoxaparin, polypeptide chain, dmTAF1, House, Taf230, susceptible, Gene Products, Mus musculus domesticus, Misinformations, Mice, TAF250, protoplasm, study, Taf200, dTAF[[II]]250, protoplast, cell, Swiss, ligand, Taf1p, inflammation, ridges, heparinum, Transplant Donors, Communication Programs, dTAF250, Innate Inflammatory Response, alpha-Heparin, Extracellular, Ovum Donor, TAF, laminae, Heparin Sodium, Organ, Personal Communication, agonista, inhibitors, TAF[[II]]250, findings, protein complex, Apoptotic Bodies, Proteins, l(3)84Ab, BG:DS00004.13, Cell, impact-a, Vesicle, Concept, dTAF230, native protein, natural protein, Mus, p230, Communications Personnel, Protein, chemical analysis, TAF[[II]]250/230, IMPACT, imprinted and ancient gene protein homolog, TFIID, agonists, Donor, Liquaemin, Sodium, unresponsive, Unfractionated, Exovesicle, flange, Mus musculus., organ process, agoniste, antagonists, Taf[[II]]250, alpha Heparin, TAF[[II]]230, Organ Donor, donneur, increased number, House Mice, TAF[II]250, Body, Miscommunications, Laboratory Mice, Protein Gene Products, Parnaparin, processes, present in greater numbers in organism, Gene Proteins, DmelCG17603, signalling process, Innate Inflammatory Responses, assay, responsive, Heparin, Laboratory Mouse, RWDD5, Fluxum, TAF1nucleocytoplasm, Inflammations, determination, Laboratory, Mus domesticus, Heparinic acid, CASP-14, Extracellular Vesicle, neutral molecular compounds, House Mouse, dmTAF[[II]]230, heparina, Personal, heparine, Communications, Roles, Sandoparin, symptoms, Concepts, Donator, Miscommunication, molecule, molecula, imprinted and ancient gene protein, Heparinic Acid, molecules, inflammatory response, TFIID TAF250, cel, Personnel, Tissue, Swiss Mice, Social Communications, Molekuel, Communication, Social, Cy 222, Reviparin, Role Concepts, Tissue Donor, intracellular, single organism signaling, screening, dTAF[[II]]230, Transplant Donor, Unfractionated Heparin, Social Communication, Transplant, mouse, TAF200, Semen Donors, TAFII-250, TAF250/230, Programs, Bemiparin, Program, TAFII250, Role Concept, Playthings and Play, agonist, Apoptotic, Mini-ICE, Role, Plaything, Donors, internal to cell, activation, Mus musculus, Caspase-14 subunit p10, mice, Swiss Mouse, Toys, signs, Pathologic, Caspase-14 subunit p19, CG17603, MICE, TAF[[II]], Semen Donor, domesticus, Semen, Taf250, antagonists and inhibitors, SR3-5, Mouse, Communication Program, Sodium Heparin, E430016J11Rik, Ovum, Ovum Donors, Organ Donors, Innate, TAF230, Misinformation, 3.4.22.-, Inflammatory Response, d230, Plays, Exovesicles, Apoptotic Body, Bodies, Processes, Vesicles, dTAFII250, mini-ICE, Ximpact, EfW1, Certoparin, Enoxaparin, dmTAF1, House, Taf230, Mus musculus domesticus, Misinformations, Mice, Toy, TAF250, protoplasm, study, Taf200, dTAF[[II]]250, protoplast, Playthings, cell, Swiss, Taf1p, inflammation, heparinum, Transplant Donors, Communication Programs, dTAF250, Puppets, Innate Inflammatory Response, alpha-Heparin, Extracellular, Play, Ovum Donor, TAF, Puppet, Heparin Sodium, Organ, Personal Communication, agonista, inhibitors, TAF[[II]]250, findings, Apoptotic Bodies, l(3)84Ab, BG:DS00004.13, Cell, impact-a, Vesicle, Concept, dTAF230, Mus, p230, Communications Personnel, chemical analysis, TAF[[II]]250/230, IMPACT, imprinted and ancient gene protein homolog, TFIID, agonists, Donor, Liquaemin, Sodium, Pathological, Unfractionated, Exovesicle, Mus musculus., agoniste, antagonists, Taf[[II]]250, alpha Heparin, TAF[[II]]230, Organ Donor, donneur, House Mice, TAF[II]250, Pathological Processes, Body, Miscommunications, Laboratory Mice, Parnaparin, DmelCG17603, signalling process, Innate Inflammatory Responses, assay, Heparin, Laboratory Mouse, RWDD5, Fluxum, TAF1Networks, SLAP-2, Bru, 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1053/14, Zinc Cysteinate, Modern, Metrs, CG5723, 2-Amino-4-(methylthio)butyric acid, StF-IT-1, Th, Search, l(3)05309, Cys, Source Softwares, Software Tools, METRS, Programs, ACMICD, Program, Computer Applications, TPSG1, S-adenosyl-L-methionine:thiol S-methyltransferase activity, HCD, DL1, Ionen, NF-E1, Computer Applications Software, lysine, Computer Applications Softwares, Methionin, median, Hmet, Softwares, (2R)-2-amino-3-sulfanylpropanoic acid, Filiation, fixed, MILD1, baseline reference sample, Software Applications, HLA-DR-associated protein II, DI-2, MS/MS, Source Software, DmelCG3619, I-2Dm, Mars, common, MASCOT, L-Cysteine, CG4299, alpha, MASS, 1304/03, human, CT12133, L-Cystein, I-2PP1, dhrp/gkap, Life Cycles, Mtrns, sample., Applications, TAF-IBETA, label, PRSS31, 2017, TAF-Ibeta, MTRNS, Polypeptide, MARS, l(3)92Ab, TMT, i2pp2a, Liquimeth, Computer Software Applications, l(3)j8C3, non-neoplastic sample, human being, 5301, 2-amino-4-(methylsulfanyl)butanoic acid, Cysteine Hydrochloride, Family Member, AW549739, anon-WO0118547.269, CG17064, L Isomer, L-Zystein, FBN, Gene, Ten[m], Network, Computer, thomson, protein-containing complex, PHAPII, Human, mass-to-charge ratio, Odz, Homo sapiens, polypeptide chain, ECTOL1, Gene Products, L-Methionine, Del(8)44H, Lysine, Half-Cystine, Man, Pedameth, Application, C20orf156, Open Source Softwares, Search Engines, odz, 1119/09, Research, MS2, L Cysteine, Software Application, iones, E-920, MRS, ipp2a2, INO80S, Open Source Software, 2pp2a, SPG70, Sciences, Hcys, ions, man, l(3)rJ307, CG10574, Computer Software Application, OCTD, mKIAA0989, Src-like adapter protein 2, l(3)05301, 2PP2A, 2-amino-4-(methylthio)butanoic acid, 10^[-6], Tools, CYSTEINE, LMPY, taf-ibeta, odz/ten-m, dSET, dSet, FREE CYSTEINE, dmDelta, peptidos, Kinship Networks, (2R)-2-amino-3-mercaptopropanoic acid, metionina, Family, thiol methyltransferase activity, Phobos, Controlled, Applications Software, germline reference sample, Open Source, data, Controlling, Computer Software, l(3)05151, Family Research, DL-Methionine, protein complex, Proteins, 1440/11, igaad, backward, L-Isomer, Peptide, Engine, native sample, group, Ten79E, Tool, Family Members, polypeptide, Software Tool, native protein, natural protein, I-2PP2A, Acetate, Dm I-2, Protein, 0495/20, I2PP2A, MFS1, MIXL, L-Lysine, Software, tandem MS, Zystein, Data Base, Met, WMS2, Col4a-1, CT16449, ensemble, 2-amino-3-sulfanylpropanoic acid, prophylaxis, 1423/11, Engineering, L-2-Amino-3-mercaptopropionic acid, (R)-2-amino-3-mercaptopropanoic acid, E(ls)2, inherited reference sample, 2-Amino-3-mercaptopropionic acid, sample population, Protein Gene Products, Computer Programs, Gene Proteins, dSET/TAF-Ibeta, Deimos, 2610030F17Rik, Applications Softwares, 1485/04, Ion, Modulator of antigen receptor signaling, control, Families, Modern Man, SSKS, alpha-amino-gamma-methylmercaptobutyric acid, E920, ten(m), Peptid, variable, AA407739, 6-diaminohexanoic acid, Relatives, l(3)00844, Enisyl, CG11452, reversedInflammatory Response, Innate Inflammatory Responses., Exovesicles, inflammatory response, Inflammations, Apoptotic Body, Bodies, Apoptotic Bodies, Vesicles, inflammation, Extracellular Vesicle, Body, Cell, microparticle, Concept, Vesicle, Role Concept, Innate Inflammatory Response, Roles, Extracellular, Role Concepts, Apoptotic, Role, Concepts, Innate, ExovesiclefalseThe Role of Extracellular Vesicle Fusion with Target Cells in Triggering Systemic InflammationExtracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis revealed that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-B. While receptor antagonists were unable to inhibit NF-B activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.2024-02-212023-12-21PXD048039NEWT:1773NEWT:3555NEWT:1182590NEWT:10090NEWT:749200NEWT:35554NEWT:4120NEWT:5693NEWT:347515NEWT:1216979NEWT:307972NEWT:92867NEWT:990346NEWT:544496NEWT:5334NEWT:145953NEWT:284812NEWT:115104NEWT:43330NEWT:67825NEWT:44544NEWT:13076NEWT:544404NEWT:3702NEWT:8839NEWT:4232NEWT:1736309NEWT:4113NEWT:7227NEWT:11298NEWT:885318NEWT:4081NEWT:876138NEWT:554NEWT:5691NEWT:260710NEWT:106592NEWT:237561NEWT:9913NEWT:10036NEWT:4100NEWT:7574NEWT:1351NEWT:1076NEWT:6763NEWT:7215NEWT:380394NEWT:272563NEWT:1639NEWT:188229NCBITaxon:79857NEWT:746360NEWT:6239NEWT:135588NEWT:135622NEWT:6915NEWT:9986NEWT:101510NEWT:3880NEWT:58002NEWT:9103NEWT:4577NEWT:146479NEWT:1000589NEWT:145943NEWT:85962NEWT:160488NEWT:317447NEWT:3635NEWT:7955NCBITaxon:2NEWT:7959NEWT:2261NEWT:3197NEWT:9615NEWT:884019NEWT:4565NEWT:1264690NEWT:169963NCBITaxon:38727NEWT:36329NEWT:34305NEWT:59729NCBITaxon:183674NEWT:626528NEWT:139927NEWT:4558NEWT:9606NEWT:367830NEWT:243230NEWT:931281NEWT:7029NEWT:1283300NEWT:334747NEWT:470NCBITaxon:79824NCBITaxon:4563NEWT:3218NEWT:5759NEWT:9838NCBITaxon:9615NEWT:1736231NEWT:1193501NEWT:6287NEWT:6326NEWT:9796NEWT:2762NEWT:5476NEWT:562NEWT:260707NEWT:287NEWT:10117NEWT:10116NEWT:1280NEWT:1836NEWT:29760NEWT:260705NEWT:1148NEWT:4932NEWT:70448NEWT:9825NEWT:3603NEWT:698936NEWT:39946NEWT:11676NEWT:9823NEWT:100226NCBITaxon:6073NEWT:4896NEWT:6279NEWT:7370NEWT:573NEWT:6282NEWT:709138326335