Nature 341, 57 - 59 (07 September 1989); doi:10.1038/341057a0

Intercellular adhesion molecule-1 is an endothelial cell adhesion receptor for Plasmodium falciparum

A. R. Berendt, D. L. Simmons^*, J. Tansey, C. I. Newbold & K. Marsh

Molecular Parasitology Group Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, UK
^*Imperial Cancer Research Fund, Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford 0X3 9DU, UK

THE primary event in the pathogenesis of severe malaria in Plasmodium falciparum infection is thought fo be adherence of trophozoite- and schizont-infected erythrocytes to capillary endothelium¹, a process called sequestration. Identifying the endothelial molecules used as receptors is an essential step in understanding this disease process. Recent work implicates the membrane glycoprotein CD36 (platelet glycoprotein IV; refs 2–5) and the multi-functional glycoprotein thrombospondin⁶ as receptors. Although CD36 has a widespread distribution on microvas-cular endothelium⁷, it may not be expressed on all capillary beds where sequestration occurs, especially in the brain⁸. The role of thrombospondin in cell adhesion,in vitro or in vivo, is less certain^4,9. We have noticed that some parasites bind to human umbilical-vein endothelial cells independently of CD36 or thrombospondin. To screen for alternative receptors, we have developed a novel cell-adhesion assay using transfected COS cells, which confirms that CD36 is a cell-adhesion receptor. In addition, we find that an endothelial-binding line of P. falciparum binds to COS cells transfected with a complementary DNA encoding intercellular adhesion molecule-1. As this molecule is widely distributed on capillaries and is inducible¹⁰, this finding may be relevant to the pathogenesis of severe malaria.

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