The role of extracellular vesicle fusion with target cells in triggering systemic inflammation.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 Feb 2024
Historique:
received: 17 07 2023
accepted: 16 01 2024
medline: 8 2 2024
pubmed: 8 2 2024
entrez: 7 2 2024
Statut: epublish

Résumé

Extracellular 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.

Identifiants

pubmed: 38326335
doi: 10.1038/s41467-024-45125-1
pii: 10.1038/s41467-024-45125-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1150

Subventions

Organisme : Crafoordska Stiftelsen (Crafoord Foundation)
ID : 20180506 and 202110908
Organisme : Vetenskapsrådet (Swedish Research Council)
ID : 2019-01086

Informations de copyright

© 2024. The Author(s).

Références

Talamonti, G., D’Aliberti, G. & Cenzato, M. Aulus cornelius celsus and the head injuries. World Neurosurg. 133, 127–134 (2020).
pubmed: 31568909 doi: 10.1016/j.wneu.2019.09.119
Huber-Lang, M., Lambris, J. D. & Ward, P. A. Innate immune responses to trauma. Nat. Immunol. 19, 327–341 (2018).
pubmed: 29507356 pmcid: 6027646 doi: 10.1038/s41590-018-0064-8
Chousterman, B. G., Swirski, F. K. & Weber, G. F. Cytokine storm and sepsis disease pathogenesis. Semin. Immunopathol. 39, 517–528 (2017).
pubmed: 28555385 doi: 10.1007/s00281-017-0639-8
Hoesel, B. & Schmid, J. A. The complexity of NF-kappaB signaling in inflammation and cancer. Mol. Cancer 12, 86 (2013).
pubmed: 23915189 pmcid: 3750319 doi: 10.1186/1476-4598-12-86
Frohlich, M. et al. Temporal phenotyping of circulating microparticles after trauma: a prospective cohort study. Scand. J. Trauma Resusc. Emerg. Med 26, 33 (2018).
Boscolo, A. et al. Levels of circulating microparticles in septic shock and sepsis-related complications: a case-control study. Minerva Anestesiol. 85, 625–634 (2019).
pubmed: 30481997 doi: 10.23736/S0375-9393.18.12782-9
Sabatier, F. et al. Interaction of endothelial microparticles with monocytic cells in vitro induces tissue factor-dependent procoagulant activity. Blood 99, 3962–3970 (2002).
pubmed: 12010795 doi: 10.1182/blood.V99.11.3962
Burger, D. et al. Microparticles: biomarkers and beyond. Clin. Sci. (Lond.) 124, 423–441 (2013).
pubmed: 23249271 doi: 10.1042/CS20120309
Cognasse, F. et al. The role of microparticles in inflammation and transfusion: A concise review. Transfus. Apher. Sci. 53, 159–167 (2015).
pubmed: 26584596 doi: 10.1016/j.transci.2015.10.013
Rizo, J. & Sudhof, T. C. Snares and Munc18 in synaptic vesicle fusion. Nat. Rev. Neurosci. 3, 641–653 (2002).
pubmed: 12154365 doi: 10.1038/nrn898
Atai, N. A. et al. Heparin blocks transfer of extracellular vesicles between donor and recipient cells. J. Neurooncol 115, 343–351 (2013).
pubmed: 24002181 doi: 10.1007/s11060-013-1235-y
Shen, C. et al. The trans-SNARE-regulating function of Munc18-1 is essential to synaptic exocytosis. Nat. Commun. 6, 8852 (2015).
pubmed: 26572858 doi: 10.1038/ncomms9852
Yu, H. et al. SNARE zippering requires activation by SNARE-like peptides in Sec1/Munc18 proteins. Proc. Natl Acad. Sci. USA 115, E8421–e8429 (2018).
pubmed: 30127032 pmcid: 6130351 doi: 10.1073/pnas.1802645115
Mause, S. F. & Weber, C. Microparticles: protagonists of a novel communication network for intercellular information exchange. Circ. Res 107, 1047–1057 (2010).
pubmed: 21030722 doi: 10.1161/CIRCRESAHA.110.226456
De Paoli, S. H. et al. Dissecting the biochemical architecture and morphological release pathways of the human platelet extracellular vesiculome. Cell Mol. Life Sci. 75, 3781–3801 (2018).
pubmed: 29427073 doi: 10.1007/s00018-018-2771-6
Chimen, M. et al. Appropriation of GPIbalpha from platelet-derived extracellular vesicles supports monocyte recruitment in systemic inflammation. Haematologica 105, 1248–1261 (2020).
pubmed: 31467123 pmcid: 7193470 doi: 10.3324/haematol.2018.215145
Prescott, J. A., Mitchell, J. P. & Cook, S. J. Inhibitory feedback control of NF-kappaB signalling in health and disease. Biochem J. 478, 2619–2664 (2021).
pubmed: 34269817 doi: 10.1042/BCJ20210139
Kadkova, A., Radecke, J. & Sorensen, J. B. The SNAP-25 Protein Family. Neuroscience 420, 50–71 (2019).
pubmed: 30267828 doi: 10.1016/j.neuroscience.2018.09.020
Oehmcke, S. et al. Stimulation of blood mononuclear cells with bacterial virulence factors leads to the release of pro-coagulant and pro-inflammatory microparticles. Cell Microbiol 14, 107–119 (2012).
pubmed: 21951918 doi: 10.1111/j.1462-5822.2011.01705.x
Verhage, M. et al. Synaptic assembly of the brain in the absence of neurotransmitter secretion. Science 287, 864–869 (2000).
pubmed: 10657302 doi: 10.1126/science.287.5454.864
Wada, K., Hosokawa, K., Ito, Y. & Maeda, M. Effects of ROCK inhibitor Y-27632 on cell fusion through a microslit. Biotechnol. Bioeng. 112, 2334–2342 (2015).
pubmed: 25952096 doi: 10.1002/bit.25641
Futosi, K., Fodor, S. & Mocsai, A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int. Immunopharmacol. 17, 638–650 (2013).
pubmed: 23994464 pmcid: 3827506 doi: 10.1016/j.intimp.2013.06.034
Verstrepen, L. et al. TLR-4, IL-1R and TNF-R signaling to NF-kappaB: variations on a common theme. Cell Mol. Life Sci. 65, 2964–2978 (2008).
pubmed: 18535784 doi: 10.1007/s00018-008-8064-8
Casella, J. F., Flanagan, M. D. & Lin, S. Cytochalasin D inhibits actin polymerization and induces depolymerization of actin filaments formed during platelet shape change. Nature 293, 302–305 (1981).
pubmed: 7196996 doi: 10.1038/293302a0
Wen, P. J. et al. Actin dynamics provides membrane tension to merge fusing vesicles into the plasma membrane. Nat. Commun. 7, 12604 (2016).
pubmed: 27576662 pmcid: 5013665 doi: 10.1038/ncomms12604
Kowal, J., Tkach, M. & Thery, C. Biogenesis and secretion of exosomes. Curr. Opin. Cell Biol. 29, 116–125 (2014).
pubmed: 24959705 doi: 10.1016/j.ceb.2014.05.004
Picca, A. et al. Extracellular vesicles and damage-associated molecular patterns: a Pandora’s box in health and disease. Front. Immunol. 11, 601740 (2020).
pubmed: 33304353 pmcid: 7701251 doi: 10.3389/fimmu.2020.601740
Hung, Y. et al. The exosomal compartment protects epidermal growth factor receptor from small molecule inhibitors. Biochem. Biophys. Res Commun. 510, 42–47 (2019).
pubmed: 30683316 doi: 10.1016/j.bbrc.2018.12.187
Jiang, C. Y. et al. The potential role of circulating exosomes in protecting myocardial injury in acute myocardial infarction via regulating miR-190a-3p/CXCR4/CXCL12 pathway. J. Bioenerg. Biomembr. 54, 175–189 (2022).
pubmed: 35867293 doi: 10.1007/s10863-022-09944-5
Zeng, F. & Morelli, A. E. Extracellular vesicle-mediated MHC cross-dressing in immune homeostasis, transplantation, infectious diseases, and cancer. Semin Immunopathol. 40, 477–490 (2018).
pubmed: 29594331 pmcid: 6162176 doi: 10.1007/s00281-018-0679-8
Johnston, A. et al. A systematic review of clinical practice guidelines on the use of low molecular weight heparin and fondaparinux for the treatment and prevention of venous thromboembolism: Implications for research and policy decision-making. PLoS One 13, e0207410 (2018).
pubmed: 30412622 pmcid: 6226206 doi: 10.1371/journal.pone.0207410
Kearon, C. et al. Antithrombotic therapy for VTE disease: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of American College of chest physicians evidence-based clinical practice guidelines. Chest 141, e419S–e496S (2012).
pubmed: 22315268 pmcid: 3278049 doi: 10.1378/chest.11-2301
Hull, R. D. Treatment of pulmonary embolism: The use of low-molecular-weight heparin in the inpatient and outpatient settings. Thromb. Haemost. 99, 502–510 (2008).
pubmed: 18327398 doi: 10.1160/TH07-08-0500
Shore-Lesserson, L. et al. The society of thoracic surgeons, the society of cardiovascular anesthesiologists, and the american society of extracorporeal technology: clinical practice guidelines-anticoagulation during cardiopulmonary bypass. Ann. Thorac. Surg. 105, 650–662 (2018).
pubmed: 29362176 doi: 10.1016/j.athoracsur.2017.09.061
Mousavi, S., Moradi, M., Khorshidahmad, T. & Motamedi, M. Anti-Inflammatory Effects of Heparin and Its Derivatives: A Systematic Review. Adv. Pharm. Sci. 2015, 507151 (2015).
Borsig, L. Heparin as an inhibitor of cancer progression. Prog. Mol. Biol. Transl. Sci. 93, 335–349 (2010).
pubmed: 20807651 doi: 10.1016/S1877-1173(10)93014-7
Qiu, M. et al. Pharmacological and clinical application of heparin progress: An essential drug for modern medicine. Biomed. Pharmacother. 139, 111561 (2021).
pubmed: 33848775 doi: 10.1016/j.biopha.2021.111561
Gong, J., Jaiswal, R., Dalla, P., Luk, F. & Bebawy, M. Microparticles in cancer: A review of recent developments and the potential for clinical application. Semin. Cell Dev. Biol. 40, 35–40 (2015).
pubmed: 25843775 doi: 10.1016/j.semcdb.2015.03.009
Rosell, A. et al. Patients with COVID-19 have elevated levels of circulating extracellular vesicle tissue factor activity that is associated with severity and mortality-brief report. Arterioscler Thromb. Vasc. Biol. 41, 878–882 (2021).
pubmed: 33267656 doi: 10.1161/ATVBAHA.120.315547
Ayerbe, L., Risco, C. & Ayis, S. The association between treatment with heparin and survival in patients with Covid-19. J. Thromb. Thrombolysis 50, 298–301 (2020).
pubmed: 32476080 pmcid: 7261349 doi: 10.1007/s11239-020-02162-z
Miesbach, W. & Makris, M. COVID-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin. Appl Thromb. Hemost. 26, 1076029620938149 (2020).
pubmed: 32677459 pmcid: 7370334 doi: 10.1177/1076029620938149
Xia, B. et al. Extracellular vesicles mediate antibody-resistant transmission of SARS-CoV-2. Cell Discov. 9, 2 (2023).
Abraham, E. et al. Efficacy and safety of monoclonal antibody to human tumor necrosis factor alpha in patients with sepsis syndrome. A randomized, controlled, double-blind, multicenter clinical trial. TNF-alpha MAb Sepsis Study Group. JAMA 273, 934–941 (1995).
pubmed: 7884952 doi: 10.1001/jama.1995.03520360048038
Fisher, C. J. Jr et al. Recombinant human interleukin 1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis Syndrome Study Group. JAMA 271, 1836–1843 (1994).
pubmed: 8196140 doi: 10.1001/jama.1994.03510470040032

Auteurs

Praveen Papareddy (P)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. praveen.papareddy@med.lu.se.

Ines Tapken (I)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
SMATHERIA gGmbH - Non-Profit Biomedical Research Institute, Hannover, Germany.
Center for Systems Neuroscience (ZSN), Hannover, Germany.

Keshia Kroh (K)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.

Ravi Kiran Varma Bhongir (RK)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Milladur Rahman (M)

Section of Surgery, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Maria Baumgarten (M)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Eda Irem Cim (EI)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Lilla Györffy (L)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Emanuel Smeds (E)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Ariane Neumann (A)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.

Srinivas Veerla (S)

Division of Oncology and Pathology, Lund, Department of Clinical Sciences, Lund University, Lund, Sweden.

Jon Olinder (J)

Division of Infection Medicine, Helsingborg Hospital and Department of Clinical Sciences Helsingborg, Lund University, Lund, Sweden.

Henrik Thorlacus (H)

Section of Surgery, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Cecilia Ryden (C)

Division of Infection Medicine, Helsingborg Hospital and Department of Clinical Sciences Helsingborg, Lund University, Lund, Sweden.

Eva Bartakova (E)

Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Praha, Czech Republic.

Michal Holub (M)

Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Praha, Czech Republic.

Heiko Herwald (H)

Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. heiko.hewald@med.lu.se.

Classifications MeSH