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Release of sequestered malaria parasites upon injection of a glycosaminoglycan.

ABSTRACT: 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 mug of dGAG. We suggest dGAGs to be promising candidates for adjunct therapy in severe malaria.

SUBMITTER: Vogt AM

PROVIDER: S-EPMC1579244 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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Release of sequestered malaria parasites upon injection of a glycosaminoglycan.

Vogt Anna M AM Pettersson Fredrik F Moll Kirsten K Jonsson Cathrine C Normark Johan J Ribacke Ulf U Egwang Thomas G TG Ekre Hans-Peter HP Spillmann Dorothe D Chen Qijun Q Wahlgren Mats M

PLoS pathogens 20060901 9

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 se ...[more]

PMID: 17009869

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Release of sequestered malaria parasites upon injection of a glycosaminoglycan.

Publications

Release of sequestered malaria parasites upon injection of a glycosaminoglycan.

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