Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F12%3A00375991" target="_blank" >RIV/60077344:_____/12:00375991 - isvavai.cz</a>
Výsledek na webu
<a href="http://dx.doi.org/10.1161/ATVBAHA.111.240291" target="_blank" >http://dx.doi.org/10.1161/ATVBAHA.111.240291</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1161/ATVBAHA.111.240291" target="_blank" >10.1161/ATVBAHA.111.240291</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria
Popis výsledku v původním jazyce
The therapeutic use of defibrotide (DF) in malaria is proposed. DF blocks the induction of endothelial tissue factor-mediated coagulation by parasitized red blood cells. At a concentration achievable in vivo, DF suppresses Toll-like receptors 4 and 2 agonist-driven proinflammatory cytokine production by dendritic cells (DCs). We demonstrate that DF directly decreases platelet aggregation and blocks the alternative complement pathway further proposing that DF may act through adenosine receptors. Accordingly, we observe that DF-exposed DCs produce prostaglandin E2 and have enhanced lipopolysaccharide-induced IL-10 secretion. DF blocks parasite invasion of red blood cells and rosetting and the agglutination of parasitized red blood cells. Finally, DF abolishes oocysts development in Anopheles gambiae; in a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-? levels, and ameliorated clinical score (day 5) with a trend for increased survival.
Název v anglickém jazyce
Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria
Popis výsledku anglicky
The therapeutic use of defibrotide (DF) in malaria is proposed. DF blocks the induction of endothelial tissue factor-mediated coagulation by parasitized red blood cells. At a concentration achievable in vivo, DF suppresses Toll-like receptors 4 and 2 agonist-driven proinflammatory cytokine production by dendritic cells (DCs). We demonstrate that DF directly decreases platelet aggregation and blocks the alternative complement pathway further proposing that DF may act through adenosine receptors. Accordingly, we observe that DF-exposed DCs produce prostaglandin E2 and have enhanced lipopolysaccharide-induced IL-10 secretion. DF blocks parasite invasion of red blood cells and rosetting and the agglutination of parasitized red blood cells. Finally, DF abolishes oocysts development in Anopheles gambiae; in a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-? levels, and ameliorated clinical score (day 5) with a trend for increased survival.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
EB - Genetika a molekulární biologie
OECD FORD obor
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Návaznosti výsledku
Projekt
—
Návaznosti
Z - Vyzkumny zamer (s odkazem do CEZ)
Ostatní
Rok uplatnění
2012
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Arteriosclerosis Thrombosis and Vascular Biology
ISSN
1079-5642
e-ISSN
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Svazek periodika
32
Číslo periodika v rámci svazku
3
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
12
Strana od-do
786-798
Kód UT WoS článku
000300639300035
EID výsledku v databázi Scopus
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