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

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Main Authors: Mari Palviainen, Johanna Puutio, Rikke Halse Østergaard, Johannes A. Eble, Katariina Maaninka, Umar Butt, Joseph Ndika, Otto K. Kari, Masood Kamali‐Moghaddam, Kasper Kjaer‐Sorensen, Claus Oxvig, Ana M. Aransay, Juan M. Falcon‐Perez, Antonio Federico, Dario Greco, Saara Laitinen, Yuya Hayashi, Pia R.‐M. Siljander
Format: Artículo Open Access
Published: Wiley 2024
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author Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
author_facet Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
collection Wiley Open Access
contents Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing Mari Palviainen Johanna Puutio Rikke Halse Østergaard Johannes A. Eble Katariina Maaninka Umar Butt Joseph Ndika Otto K. Kari Masood Kamali‐Moghaddam Kasper Kjaer‐Sorensen Claus Oxvig Ana M. Aransay Juan M. Falcon‐Perez Antonio Federico Dario Greco Saara Laitinen Yuya Hayashi Pia R.‐M. Siljander Journal of Extracellular 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. 10.1002/jev2.12513 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1002/jev2.12513
format Artículo Open Access
id wiley_oa_10_1002_jev2_12513
institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by/4.0/
publishDate 2024
publisher Wiley
record_format wiley_oa
spellingShingle Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
Mari Palviainen
Johanna Puutio
Rikke Halse Østergaard
Johannes A. Eble
Katariina Maaninka
Umar Butt
Joseph Ndika
Otto K. Kari
Masood Kamali‐Moghaddam
Kasper Kjaer‐Sorensen
Claus Oxvig
Ana M. Aransay
Juan M. Falcon‐Perez
Antonio Federico
Dario Greco
Saara Laitinen
Yuya Hayashi
Pia R.‐M. Siljander
Journal of Extracellular Vesicles
Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing Mari Palviainen Johanna Puutio Rikke Halse Østergaard Johannes A. Eble Katariina Maaninka Umar Butt Joseph Ndika Otto K. Kari Masood Kamali‐Moghaddam Kasper Kjaer‐Sorensen Claus Oxvig Ana M. Aransay Juan M. Falcon‐Perez Antonio Federico Dario Greco Saara Laitinen Yuya Hayashi Pia R.‐M. Siljander Journal of Extracellular 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. 10.1002/jev2.12513 http://creativecommons.org/licenses/by/4.0/
title Beyond basic characterization and omics: Immunomodulatory roles of platelet‐derived extracellular vesicles unveiled by functional testing
topic Journal of Extracellular Vesicles
url https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12513