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Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria

Nature Medicine volume 6, pages 86–90 (2000)Cite this article

Abstract

Infection with Plasmodium falciparum during pregnancy leads to the accumulation of parasite-infected erythrocytes in the placenta1, and is associated with excess perinatal mortality, premature delivery and intrauterine growth retardation in the infant, as well as increased maternal mortality and morbidity2,3. P. falciparum can adhere to specific receptors on host cells, an important virulence factor enabling parasites to accumulate in various organs4. We report here that most P. falciparum isolates from infected placentae can bind to hyaluronic acid, a newly discovered receptor for parasite adhesion that is present on the placental lining. In laboratory isolates selected for specific high-level adhesion, binding to hyaluronic acid could be inhibited by dodecamer or larger oligosaccharide fragments or polysaccharides, treatment of immobilized receptor with hyaluronidase, or treatment of infected erythrocytes with trypsin. In vitro flow-based assays demonstrated that high levels of adhesion occurred at low wall shear stress, conditions thought to prevail in the placenta. Our findings indicate that adhesion to hyaluronic acid is involved in mediating placental parasite accumulation, thus changing the present understanding of the mechanisms of placental infection, with implications for the development of therapeutic and preventative interventions.

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Figure 1: Receptor-specific adhesion of P. falciparum isolates.
Figure 2: Adhesion of P. falciparum-infected erythrocytes to HA and CSA.
Figure 3: P. falciparum-infected erythrocytes adhere to immobilized HA under flow conditions.

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Acknowledgements

Human erythrocytes and serum were provided by the Red Cross Blood Bank (Victoria, Australia). The authors thank E. Chaluluka and R. Tembenu for assistance with sample collection and processing; C. Nicoll for assistance with flow-based adhesion assays; R.A. Childs for FPLC analysis; and C. Bradshaw, V. Lema and T. Taylor for support. Thanks also go to C. Mhango and the staff of the Antenatal Clinic and Labour Ward of the Queen Elizabeth Central Hospital (Blantyre, Malawi) for cooperation, and to all individuals who participated in the study. This study was supported by funding from the National Health and Medical Research Council of Australia, the Wellcome Trust, UK, the District 9680 Rotary Against Malaria Programme, Australia, and the Medical Research Council, UK.

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Author notes

  1. Graham V. Brown

    Present address: Department of Medicine, University of Melbourne, Victoria, Australia

Authors and Affiliations

  1. The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia

    James G. Beeson, John C. Reeder & Graham V. Brown

  2. The Wellcome Trust Research Laboratories and Malaria Project, College of Medicine, University of Malawi, Blantyre, Malawi

    Stephen J. Rogerson & Malcolm E. Molyneux

  3. The Liverpool School of Tropical Medicine, University of Liverpool, Liverpool, UK

    Stephen J. Rogerson & Malcolm E. Molyneux

  4. Department of Microbiology, Monash University, Clayton, Victoria, Australia

    Brian M. Cooke

  5. The Glycosciences Laboratory, Imperial College School of Medicine, Northwick Park Hospital, Harrow, Middlesex, UK

    Wengang Chai & Alexander M. Lawson

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  1. James G. Beeson
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Correspondence to James G. Beeson.

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Beeson, J., Rogerson, S., Cooke, B. et al. Adhesion of Plasmodium falciparum-infected erythrocytes to hyaluronic acid in placental malaria. Nat Med 6, 86–90 (2000). https://doi.org/10.1038/71582

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