PUBLICATION

Beyond basic characterization and omics: Immunomodulatory roles of platelet-derived extracellular vesicles unveiled by functional testing

Authors
Palviainen, M., Puutio, J., Østergaard, R.H., Eble, J.A., Maaninka, K., Butt, U., Ndika, J., Kari, O.K., Kamali-Moghaddam, M., Kjaer-Sorensen, K., Oxvig, C., Aransay, A.M., Falcon-Perez, J.M., Federico, A., Greco, D., Laitinen, S., Hayashi, Y., Siljander, P.R.
ID
ZDB-PUB-240928-4
Date
2024
Source
Journal of extracellular vesicles   13: e12513e12513 (Journal)
Registered Authors
Keywords
extracellular vesicles, functional assays, immunomodulatory, inflammation, innate immunity, macrophages, miRNA, platelets, protein corona
MeSH Terms
  • Humans
  • Macrophages/immunology
  • Macrophages/metabolism
  • Immunomodulation
  • Zebrafish*
  • Platelet Activation*
  • MicroRNAs/metabolism
  • Platelet Membrane Glycoproteins/metabolism
  • Extracellular Vesicles*/immunology
  • Extracellular Vesicles*/metabolism
  • Animals
  • Blood Platelets*/immunology
  • Blood Platelets*/metabolism
PubMed
39330919 Full text @ J Extracell Vesicles
Abstract
Renowned for their role in haemostasis and thrombosis, platelets are also increasingly recognized for their contribution in innate immunity, immunothrombosis and inflammatory diseases. Platelets express a wide range of receptors, which allows them to reach a variety of activation endpoints and grants them immunomodulatory functions. Activated platelets release extracellular vesicles (PEVs), whose formation and molecular cargo has been shown to depend on receptor-mediated activation and environmental cues. This study compared the immunomodulatory profiles of PEVs generated via activation of platelets by different receptors, glycoprotein VI, C-type lectin-like receptor 2 and combining all thrombin-collagen receptors. Functional assays in vivo in zebrafish and in vitro in human macrophages highlighted distinct homing and secretory responses triggered by the PEVs. In contrast, omics analyses of protein and miRNA cargo combined with physicochemical particle characterization found only subtle differences between the activated PEV types, which were insufficient to predict their different immunomodulatory functions. In contrast, constitutively released PEVs, formed in the absence of an exogenous activator, displayed a distinct immunomodulatory profile from the receptor-induced PEVs. Our findings underscore that PEVs are tunable through receptor-mediated activation. To truly comprehend their role(s) in mediating platelet functions among immune cells, conducting functional assays is imperative.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping