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Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria
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SYSNO ASEP 0375991 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria Author(s) Francischetti, I.M.B. (US)
Oliveira, C. J. (BR)
Ostera, G. R. (US)
Yager, S. B. (US)
Debierre-Grockiego, F. (DE)
Carregaro, V. (BR)
Jaramillo-Gutierrez, G. (US)
Hume, J. C. C. (US)
Jiang, L. (US)
Moretz, S. E. (US)
Lin, Ch. K. (US)
Ribeiro, J.M.C. (US)
Long, C. A. (US)
Vickers, B. K. (US)
Schwarz, R. T. (DE)
Seydel, K. B. (US)
Iacobelli, M. (IT)
Ackerman, H. C. (US)
Srinivasan, P. (US)
Gomes, R. B. (US)
Wang, X. (US)
Monteiro, R.Q. (BR)
Kotsyfakis, Michalis (BC-A) RID, ORCID
Sa-Nunes, A. (BR)
Waisberg, M. (US)Source Title Arteriosclerosis Thrombosis and Vascular Biology. - : Lippincott Williams & Wilkins - ISSN 1079-5642
Roč. 32, č. 3 (2012), s. 786-798Number of pages 12 s. Language eng - English Country US - United States Keywords anticoagulants ; blood coagulation ; endothelium ; microcirculation ; vascular biology ; malaria ; defibrotide ; inflammation Subject RIV EB - Genetics ; Molecular Biology CEZ AV0Z60220518 - PAU-O, BC-A (2005-2011) UT WOS 000300639300035 DOI 10.1161/ATVBAHA.111.240291 Annotation 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-γ levels, and ameliorated clinical score (day 5) with a trend for increased survival. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2013
Number of the records: 1