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Characterization of human placental glycosaminoglycans and regional binding to VAR2CSA in malaria infected erythrocytes

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Abstract

Placental malaria is a serious problem in sub-Saharan Africa. Young women are particular susceptible to contracting this form of malaria during their first or second pregnancy despite previously acquired immunity from past infections. Placental malaria is caused by Plasmodium falciparum parasites expressing VAR2CSA on the erythrocyte surface. This protein adheres to a low-sulfated chondroitin sulfate-A found in placental tissue causing great harm to both mother and developing fetus. In rare cases, the localization of infected erythrocytes to the placenta can even result in the vertical transmission of malaria. In an effort to better understand this infection, chondroitin sulfate was isolated from the cotyledon part of the placenta, which should be accessible for parasite adhesion, as well as two non-accessible parts of the placenta to serve as controls. The placental chondroitin sulfate structures and their VAR2CSA binding were characterized. All portions of human placenta contained sufficient amounts of the appropriate low-sulfated chondroitin sulfate-A to display high-affinity binding to a recombinant truncated VAR2CSA construct, as determined using surface plasmon resonance. The cotyledon is the only placental tissue accessible to parasites in the bloodstream, suggesting it is the primary receptor for parasite infected red blood cells.

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Abbreviations

AMAC:

2-aminoacridone

CHAPS:

3-[(3-cholamidopropyl) dimethylammonio]-1- propanesulfonate

EDTA:

ethylenediaminetetraacetic acid

GAG:

glycosaminoglycan

HEPES:

4-(2-hydroxyethyl-1-piperazineethanesulfonic acid

pfEMP:

Plasmodium falciparum erythrocyte membrane protein

SPR:

surface plasmon resonance

VAR2CSA:

a PfEMP1 protein

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Acknowledgments

This work was supported by grants from the funded by the National Institutes of Health HL101721 and HL096972.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic, Troy, NY, 12180, USA

    Julie M. Beaudet, Leandra Mansur, Bo Yang & Robert J. Linhardt

  2. Department of Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic, Troy, NY, 12180, USA

    Julie M. Beaudet, Leandra Mansur, Eun Ji Joo, Eyal Kamhi & Robert J. Linhardt

  3. Department of Chemical Engineering, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic, Troy, NY, 12180, USA

    Fuming Zhang & Robert J. Linhardt

  4. Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark

    Thomas M. Clausen & Ali Salanti

  5. Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark

    Thomas M. Clausen & Ali Salanti

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  1. Julie M. Beaudet
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  2. Leandra Mansur
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Correspondence to Robert J. Linhardt.

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Beaudet, J.M., Mansur, L., Joo, E.J. et al. Characterization of human placental glycosaminoglycans and regional binding to VAR2CSA in malaria infected erythrocytes. Glycoconj J 31, 109–116 (2014). https://doi.org/10.1007/s10719-013-9506-6

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  • DOI: https://doi.org/10.1007/s10719-013-9506-6

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