Extracellular vesicles are associated with C-reactive protein in sepsis

Abstract There is increasing evidence that C-reactive protein (CRP) can mediate inflammatory reactions following the transformation of functionally inert pentameric CRP (pCRP) into its structural isoform pCRP* and into monomeric CRP (mCRP). This conversion can occur on the membranes of apoptotic or...

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Autores principales:	Birgit Fendl, René Weiss, Tanja Eichhorn, Ingrid Linsberger, Taras Afonyushkin, Florian Puhm, Christoph J. Binder, Michael B. Fischer, Viktoria Weber
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9e92200452624ad38d6ba7c3785f5952
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spelling	oai:doaj.org-article:9e92200452624ad38d6ba7c3785f59522021-12-02T17:04:35ZExtracellular vesicles are associated with C-reactive protein in sepsis10.1038/s41598-021-86489-42045-2322https://doaj.org/article/9e92200452624ad38d6ba7c3785f59522021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-86489-4https://doaj.org/toc/2045-2322Abstract There is increasing evidence that C-reactive protein (CRP) can mediate inflammatory reactions following the transformation of functionally inert pentameric CRP (pCRP) into its structural isoform pCRP* and into monomeric CRP (mCRP). This conversion can occur on the membranes of apoptotic or activated cells or on extracellular vesicles (EVs) shed from the cell surface. Here, we characterized the association of CRP with EVs in plasma from sepsis patients using flow cytometry, and found highly elevated levels of total EV counts and CRP+ EVs as compared to healthy individuals. We further assessed the ability of PentraSorb CRP, an extracorporeal device for the adsorption of CRP, to deplete free CRP and CRP+ EVs. Treatment of septic plasma with the adsorbent in vitro resulted in almost complete removal of both, free CRP and CRP+ EVs, while total EV counts remained largely unaffected, indicating the detachment of CRP from the EV surface. EVs from septic plasma elicited a release of interleukin-8 from cultured human monocytes, which was significantly reduced by adsorbent treatment prior to EV isolation. Our findings provide evidence that CRP+ EVs exhibit pro-inflammatory characteristics and can contribute to the spreading of inflammation throughout the circulation on top of their pro-coagulant activity.Birgit FendlRené WeissTanja EichhornIngrid LinsbergerTaras AfonyushkinFlorian PuhmChristoph J. BinderMichael B. FischerViktoria WeberNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Birgit Fendl René Weiss Tanja Eichhorn Ingrid Linsberger Taras Afonyushkin Florian Puhm Christoph J. Binder Michael B. Fischer Viktoria Weber Extracellular vesicles are associated with C-reactive protein in sepsis
description	Abstract There is increasing evidence that C-reactive protein (CRP) can mediate inflammatory reactions following the transformation of functionally inert pentameric CRP (pCRP) into its structural isoform pCRP* and into monomeric CRP (mCRP). This conversion can occur on the membranes of apoptotic or activated cells or on extracellular vesicles (EVs) shed from the cell surface. Here, we characterized the association of CRP with EVs in plasma from sepsis patients using flow cytometry, and found highly elevated levels of total EV counts and CRP+ EVs as compared to healthy individuals. We further assessed the ability of PentraSorb CRP, an extracorporeal device for the adsorption of CRP, to deplete free CRP and CRP+ EVs. Treatment of septic plasma with the adsorbent in vitro resulted in almost complete removal of both, free CRP and CRP+ EVs, while total EV counts remained largely unaffected, indicating the detachment of CRP from the EV surface. EVs from septic plasma elicited a release of interleukin-8 from cultured human monocytes, which was significantly reduced by adsorbent treatment prior to EV isolation. Our findings provide evidence that CRP+ EVs exhibit pro-inflammatory characteristics and can contribute to the spreading of inflammation throughout the circulation on top of their pro-coagulant activity.
format	article
author	Birgit Fendl René Weiss Tanja Eichhorn Ingrid Linsberger Taras Afonyushkin Florian Puhm Christoph J. Binder Michael B. Fischer Viktoria Weber
author_facet	Birgit Fendl René Weiss Tanja Eichhorn Ingrid Linsberger Taras Afonyushkin Florian Puhm Christoph J. Binder Michael B. Fischer Viktoria Weber
author_sort	Birgit Fendl
title	Extracellular vesicles are associated with C-reactive protein in sepsis
title_short	Extracellular vesicles are associated with C-reactive protein in sepsis
title_full	Extracellular vesicles are associated with C-reactive protein in sepsis
title_fullStr	Extracellular vesicles are associated with C-reactive protein in sepsis
title_full_unstemmed	Extracellular vesicles are associated with C-reactive protein in sepsis
title_sort	extracellular vesicles are associated with c-reactive protein in sepsis
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9e92200452624ad38d6ba7c3785f5952
work_keys_str_mv	AT birgitfendl extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT reneweiss extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT tanjaeichhorn extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT ingridlinsberger extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT tarasafonyushkin extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT florianpuhm extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT christophjbinder extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT michaelbfischer extracellularvesiclesareassociatedwithcreactiveproteininsepsis AT viktoriaweber extracellularvesiclesareassociatedwithcreactiveproteininsepsis
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Extracellular vesicles are associated with C-reactive protein in sepsis

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