Phenotypic characterization of acoustically enriched extracellular vesicles from pathogen-activated platelets
(2023) In Journal of Innate Immunity- Abstract
Extracellular vesicles (EVs) are derived from the membrane of platelets and released in the circulation upon activation or injury. Analogous to the parent cell, platelet derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increases in several pathological inflammatory diseases, such as sepsis. We have previously reported that the M1 protein released from the bacterial pathogen Streptococcus pyogenes directly mediates platelet activation. In this study, EVs were isolated from these pathogen-activated platelets using acoustic trapping and their inflammation phenotype was characterized using quantitative mass spectrometry-based... (More)
Extracellular vesicles (EVs) are derived from the membrane of platelets and released in the circulation upon activation or injury. Analogous to the parent cell, platelet derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increases in several pathological inflammatory diseases, such as sepsis. We have previously reported that the M1 protein released from the bacterial pathogen Streptococcus pyogenes directly mediates platelet activation. In this study, EVs were isolated from these pathogen-activated platelets using acoustic trapping and their inflammation phenotype was characterized using quantitative mass spectrometry-based proteomics and cell-based models of inflammation. We determined that M1 protein mediated release of platelet derived EVs that contained the M1 protein. The isolated EVs derived from pathogen-activated platelets contained a similar protein cargo to those from physiologically activated platelets (thrombin), and included platelet membrane proteins, granule proteins and cytoskeletal proteins, coagulation factors and immune mediators. Immunomodulatory cargo, complement proteins and IgG3, were significantly enriched in EVs isolated from M1 protein-stimulated platelets. Acoustically enriched EVs were functionally intact and exhibited proinflammatory effects on addition to blood, including platelet-neutrophil complex formation, neutrophil activation, and cytokine release. Collectively, our findings reveal novel aspects of pathogen-mediated platelet activation during invasive streptococcal infection.
(Less)
- author
- Palm, Frida
LU
; Broman, Axel
LU
; Marcoux, Genevieve
LU
; Semple, John W
LU
; Laurell, Thomas L
LU
; Malmström, Johan
LU
and Shannon, Oonagh LU
- organization
-
- Immunomodulatory effects of platelets during inflammation and infection (research group)
- Department of Biomedical Engineering
- NanoLund: Centre for Nanoscience
- MultiPark: Multidisciplinary research focused on Parkinson´s disease
- LTH Profile Area: Engineering Health
- LTH Profile Area: Nanoscience and Semiconductor Technology
- LU Profile Area: Light and Materials
- Division of Hematology and Transfusion Medicine
- Platelet Immunology (research group)
- Acoustofluidics group (research group)
- SEBRA Sepsis and Bacterial Resistance Alliance (research group)
- LUCC: Lund University Cancer Centre
- Infection Medicine (BMC)
- Infection Medicine Proteomics (research group)
- epIgG (research group)
- Mass Spectrometry
- BioMS (research group)
- publishing date
- 2023-05-27
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Journal of Innate Immunity
- publisher
- Karger
- external identifiers
-
- pmid:37245510
- ISSN
- 1662-811X
- DOI
- 10.1159/000531266
- language
- English
- LU publication?
- yes
- additional info
- The Author(s). Published by S. Karger AG, Basel.
- id
- de3d78ff-9b26-4242-9249-bdf2537350ee
- date added to LUP
- 2023-06-05 13:25:49
- date last changed
- 2023-08-02 02:28:07
@article{de3d78ff-9b26-4242-9249-bdf2537350ee, abstract = {{<p>Extracellular vesicles (EVs) are derived from the membrane of platelets and released in the circulation upon activation or injury. Analogous to the parent cell, platelet derived EVs play an important role in hemostasis and immune responses by transfer of bioactive cargo from the parent cells. Platelet activation and release of EVs increases in several pathological inflammatory diseases, such as sepsis. We have previously reported that the M1 protein released from the bacterial pathogen Streptococcus pyogenes directly mediates platelet activation. In this study, EVs were isolated from these pathogen-activated platelets using acoustic trapping and their inflammation phenotype was characterized using quantitative mass spectrometry-based proteomics and cell-based models of inflammation. We determined that M1 protein mediated release of platelet derived EVs that contained the M1 protein. The isolated EVs derived from pathogen-activated platelets contained a similar protein cargo to those from physiologically activated platelets (thrombin), and included platelet membrane proteins, granule proteins and cytoskeletal proteins, coagulation factors and immune mediators. Immunomodulatory cargo, complement proteins and IgG3, were significantly enriched in EVs isolated from M1 protein-stimulated platelets. Acoustically enriched EVs were functionally intact and exhibited proinflammatory effects on addition to blood, including platelet-neutrophil complex formation, neutrophil activation, and cytokine release. Collectively, our findings reveal novel aspects of pathogen-mediated platelet activation during invasive streptococcal infection.</p>}}, author = {{Palm, Frida and Broman, Axel and Marcoux, Genevieve and Semple, John W and Laurell, Thomas L and Malmström, Johan and Shannon, Oonagh}}, issn = {{1662-811X}}, language = {{eng}}, month = {{05}}, publisher = {{Karger}}, series = {{Journal of Innate Immunity}}, title = {{Phenotypic characterization of acoustically enriched extracellular vesicles from pathogen-activated platelets}}, url = {{http://dx.doi.org/10.1159/000531266}}, doi = {{10.1159/000531266}}, year = {{2023}}, }