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Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence

Nature volume 318, pages 64–66 (1985)Cite this article

Abstract

Plasmodium falciparum infected erythrocytes containing mature trophozoites and schizonts sequester along venular endothelium1 and are not in the peripheral circulation of patients with malaria. Knobs appear on infected erythrocytes and are the points of attachment to endothelium2. Sequestration may protect the parasite from splenic destruction3 and may play a role in the pathogenesis of cerebral malaria4. Correlates of sequestration have been developed in vitro using cultured human endothelium5 and an amelanotic melanoma cell line6. Knobless strains (K−) of P. falciparum fail to sequester in vivo and to bind to cells in vitro. We now present evidence that the receptor for cytoadherence is the glycoprotein, thrombospondin. Aotus monkey or human erythrocytes containing knobby (K+) but not Aotus erythrocytes containing knobless strains of P. falciparum bind to immobilized thrombospondin. Neither binds to the adhesive proteins laminin, fibronectin, factor VIII/von Wi lie brand factor or vitronectin. Both soluble thrombospondin and anti-thrombospondin antibodies inhibit binding of parasitized Aotus erythrocytes to immobilize thrombospondin and to melanoma cells which secrete thrombospondin.

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Authors and Affiliations

  1. Laboratory of Structural Biology, National Institute of Arthritis, Diabetes, and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, 20205, USA

    David D. Roberts, Steven L. Spitalnik & Victor Ginsburg

  2. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20205, USA

    James A. Sherwood, Lindsey J. Panton, Russell J. Howard & Louis H. Miller

  3. Department of Biological Chemistry, Division of Laboratory Medicine, Washington University School of Medicine, St Louis, Missouri, 63110, USA

    Vishva M. Dixit & William A. Frazier

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  1. David D. Roberts
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  2. James A. Sherwood
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  5. Russell J. Howard
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  6. Vishva M. Dixit
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  7. William A. Frazier
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  9. Victor Ginsburg
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Roberts, D., Sherwood, J., Spitalnik, S. et al. Thrombospondin binds falciparum malaria parasitized erythrocytes and may mediate cytoadherence. Nature 318, 64–66 (1985). https://doi.org/10.1038/318064a0

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