Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

dc.creatorBastos, MF
dc.creatorAlbrecht, L
dc.creatorKozlowski, EO
dc.creatorLopes, SCP
dc.creatorBlanco, YC
dc.creatorCarlos, BC
dc.creatorCastineiras, C
dc.creatorVicente, CP
dc.creatorWerneck, CC
dc.creatorWunderlich, G
dc.creatorFerreira, MU
dc.creatorMarinho, CRF
dc.creatorMourao, PAS
dc.creatorPavao, MSG
dc.creatorCosta, FTM
dc.date2014
dc.dateAPR
dc.date2014-07-30T17:37:16Z
dc.date2015-11-26T16:48:27Z
dc.date2014-07-30T17:37:16Z
dc.date2015-11-26T16:48:27Z
dc.date.accessioned2018-03-28T23:34:55Z
dc.date.available2018-03-28T23:34:55Z
dc.identifierAntimicrobial Agents And Chemotherapy. Amer Soc Microbiology, v. 58, n. 4, n. 1862, n. 1871, 2014.
dc.identifier0066-4804
dc.identifier1098-6596
dc.identifierWOS:000333605600004
dc.identifier10.1128/AAC.00686-13
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/67242
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/67242
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1275153
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionSequestration of Plasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect to P. falciparum cytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.
dc.description58
dc.description4
dc.description1862
dc.description1871
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.languageen
dc.publisherAmer Soc Microbiology
dc.publisherWashington
dc.publisherEUA
dc.relationAntimicrobial Agents And Chemotherapy
dc.relationAntimicrob. Agents Chemother.
dc.rightsaberto
dc.sourceWeb of Science
dc.subjectHuman Cerebral Malaria
dc.subjectIntercellular-adhesion Molecule-1
dc.subjectMicrovascular Endothelial-cells
dc.subjectRed-blood-cells
dc.subjectIn-vitro Model
dc.subjectInfected Erythrocytes
dc.subjectParasitized Erythrocytes
dc.subjectRosette Formation
dc.subjectCurdlan Sulfate
dc.subjectHuman Placenta
dc.titleFucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion
dc.typeArtículos de revistas


Este ítem pertenece a la siguiente institución