Extracellular vesicles in Shiga toxin-mediated disease
Författare
Summary, in English
Paper I shows that once Shiga toxin is taken up by cells it is released within vesicles within minutes and does not undergo retrograde transport. Toxin could bind directly to extracellular vesicles and could transfer from the surface to the inside of the vesicle suggesting sequestration, possibly to evade the host response. This is a novel mechanism by which vesicles could protect their content while in the circulation.
Paper II investigated the importance of the toxin receptor, globotriaosylceramide (Gb3), in recipient cells for the uptake of Shiga toxin-containing extracellular vesicles by the cells and exertion of a cytotoxic effect. Various Gb3-negative and Gb3-positive cells were used showing that the recipient cell must possess endogenous Gb3 for the toxin, taken up in extracellular vesicles, to exert a toxic effect on cell viability.
Paper III investigated the pro-thrombotic and proinflammatory properties of Shiga toxin-induced blood cell-derived extracellular vesicles. These vesicles possessed more tissue factor activity and thrombin- generating activity and induced platelet aggregation. The vesicles contained pro-inflammatory cytokines and induced the release of IL-8 from endothelial cells co-incubated with monocytes.
Paper IV describes isolation procedures of blood cell- and cell culture-derived microvesicles and characterization of the vesicles by various methods including flow cytometry, electron microscopy, nanoparticle tracking, ELISA, proteomics and live cell imaging.
In summary, this thesis characterized important aspects of Shiga toxin-induced extracellular vesicles including their uptake, intracellular effects, release, and properties that can contribute to the development of hemolytic uremic syndrome.
Avdelning/ar
Publiceringsår
2021
Språk
Engelska
Publikation/Tidskrift/Serie
Lund University, Faculty of Medicine Doctoral Dissertation Series
Issue
2021:143
Fulltext
Dokumenttyp
Doktorsavhandling
Förlag
Lund University, Faculty of Medicine
Ämne
- Cell and Molecular Biology
Nyckelord
- Extracellular vesicles, Shiga toxin, EHEC, hemolytic uremic syndrome
Status
Published
Forskningsgrupp
- Pediatric Nephrology
Handledare
ISBN/ISSN/Övrigt
- ISSN: 1652-8220
- ISBN: 978-91-8021-150-5
Försvarsdatum
14 december 2021
Försvarstid
09:00
Försvarsplats
Belfragesalen, BMC D15, Klinikgatan 32 i Lund. Join by Zoom: https://lu-se.zoom.us/j/65285566723
Opponent
- Martin Bitzan (Associate professor (retired), Head)