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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Release of sequestered malaria parasites upon injection of a glycosaminoglycan
PLoS Pathogens, Volume 2, No. 9, Year 2006
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Description
Severe human malaria is attributable to an excessive sequestration of Plasmodium falciparum-infected and uninfected erythrocytes in vital organs. Strains of P. falciparum that form rosettes and employ heparan sulfate as a host receptor are associated with development of severe forms of malaria. Heparin, which is similar to heparan sulfate in that it is composed of the same building blocks, was previously used in the treatment of severe malaria, but it was discontinued due to the occurrence of serious side effects such as intracranial bleedings. Here we report to have depolymerized heparin by periodate treatment to generate novel glycans (dGAG) that lack anticoagulant-activity. The dGAGs disrupt rosettes, inhibit merozoite invasion of erythrocytes and endothelial binding of P. falciparum-infected erythrocytes in vitro, and reduce sequestration in in vivo models of severe malaria. An intravenous injection of dGAGs blocks up to 80% of infected erythrocytes from binding in the micro-vasculature of the rat and releases already sequestered parasites into circulation. P. falciparum-infected human erythrocytes that sequester in the non-human primate Macaca fascicularis were similarly found to be released in to the circulation upon a single injection of 500 lg of dGAG. We suggest dGAGs to be promising candidates for adjunct therapy in severe malaria. © 2006 Vogt et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC1579244/bin/ppat.0020100.sg001.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC1579244/bin/ppat.0020100.sg002.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC1579244/bin/ppat.0020100.sg003.pdf
Authors & Co-Authors
Vogt, Anna M.
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Pettersson, Fredrik
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Moll, Kirsten
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Jonsson, Cathrine
Sweden, Stockholm
Karolinska Universitetssjukhuset
Normark, Johan
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Ribacke, Ulf
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Egwang, Thomas Gordon
Uganda, Kampala
Med Biotech Laboratories Uganda
Ekre, Hans Peter T.
Sweden, Stockholm
Dilafor ab
Spillmann, Dorothe
Sweden, Uppsala
Uppsala Universitet
Chen, Qijun
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Wahlgren, Mats
Sweden, Stockholm
Karolinska Institutet
Sweden, Solna
Public Health Agency of Sweden
Statistics
Citations: 109
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1371/journal.ppat.0020100
ISSN:
15537366
e-ISSN:
15537374
Research Areas
Infectious Diseases