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PECAM-1/CDS31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes

Nature Medicine volume 3, pages 1405–1408 (1997)Cite this article

Abstract

Excessive binding of Plasmodium falciparum-infected red blood cells (pRBCs) to the vascular endothelium (cytoadherence) and to uninfected erythrocytes (rosetting) may lead to occlusion of the microvasculature and thereby contribute directly to the acute pathology of severe human malaria1,2. A number of endothelial receptors have been identified as targets for the pRBCs, including CD36, intercellular adhesion molecule-1 (ICAM-1) and chondroitin-4-sulfate (CSA)3–5. In vitro, CD36 is the most frequent target of strains from patients with mild as well as severe P. falciparum malaria, but is expressed at low levels on the cerebral microvasculature6 and therefore seems unlikely to be involved in the evolution of cerebral disease. Strains of P. falciparum that form rosettes are associated both with the occurrence of cerebral malaria and severe anemia7–9. Here we report that malaria-infected RBCs adhere to platelet/endothelial cell adhesion molecule-1 (PECAM-1/CD31) on the vascular endothelium. pRBCs bind to endothelial cells, to PECAM-1/CD31 transfected cells, and directly to recombinant PECAM-1/CD31 absorbed onto plastic. Soluble PECAM-1/CD31 and monoclonal antibodies specific for the amino-terminal segment of PECAM-1/CD31 (domains 1–4) blocked the binding. Interferon- γ (IFN-γ) — essential for the development of cerebral malaria in the mouse —was found to augment adhesion of human pRBCs to PECAM-1/CD31 on endothelial cell monolayers. Our results suggest that PECAM-1/CD31 is a virulence-associated endothelial receptor of P. falciparum-infected RBCs.

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Authors and Affiliations

  1. Microbiology and Tumor Biology Center, Karolinska Institutet, and Swedish Institute for Infectious Disease Control, Box 280, S-171 77, Stockholm, Sweden

    Carl Johan Treutiger, Andreas Heddini, Victor Fernandez & Mats Wahlgren

  2. Department of Pathology, New York Hospital/Cornell Medical Center, 525 East 68th Street, New York, New York, 10021, USA

    William A. Muller

Authors
  1. Carl Johan Treutiger
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  2. Andreas Heddini
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  3. Victor Fernandez
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  4. William A. Muller
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  5. Mats Wahlgren
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Correspondence to Mats Wahlgren.

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Treutiger, C., Heddini, A., Fernandez, V. et al. PECAM-1/CDS31, an endothelial receptor for binding Plasmodium falciparum-infected erythrocytes. Nat Med 3, 1405–1408 (1997). https://doi.org/10.1038/nm1297-1405

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