Thromb Haemost 1999; 81(05): 815-821
DOI: 10.1055/s-0037-1614575
Rapid Communication
Schattauer GmbH

Plasmodium Falciparum-infected Erythrocytes: A Mutational Analysis of Cytoadherence via Murine Thrombomodulin

Samia Rabhi-Sabile
1   INSERM U 353, Hôpital Saint-Louis, Paris, France
,
Marta Steiner-Mosonyi
2   From the Departments of Medicine and Medical Biophysics, University of Toronto, Canada
,
Saskia Pollefeyt
3   The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
,
Desiré Collen
3   The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
,
B. Pouvelle
4   Unité de Parasitologie Expérimentale and Faculté de Médecine, Université de la Méditerranée, Aix Marseille II, France
,
Jurg Gysin
4   Unité de Parasitologie Expérimentale and Faculté de Médecine, Université de la Méditerranée, Aix Marseille II, France
,
Marie-Claire Boffa
1   INSERM U 353, Hôpital Saint-Louis, Paris, France
,
Edward M. Conway
2   From the Departments of Medicine and Medical Biophysics, University of Toronto, Canada
3   The Center for Transgene Technology and Gene Therapy, Flanders Interuniversity Institute for Biotechnology, University of Leuven, Leuven, Belgium
› Author Affiliations
Supported in part by the Heart and Stroke Foundation of Ontario.
Dr. Conway is a Career Investigator of the Heart and Stroke Foundation of Canada. Dr. Rabhi-Sabile was supported by a Co-operative France-Belgium INSERM-MVG Medical Research Grant.
Further Information

Publication History

Received 17 November 1998

Accepted after revision 22 January 1999

Publication Date:
09 December 2017 (online)

Summary

The pathophysiologic events leading to organ damage in Plasmo-dium falciparum malaria infections involve adhesion and sequestration of parasite-infected erythrocytes (PRBC) to the vascular endothelium and syncytiotrophoblast. Several potential receptors to which the PRBCs may bind have recently been identified, one of which is thrombomodulin (TM). TM has been implicated particularly in mediating sequestration of P. falciparum-infected erythrocytes in the placenta and brain, two sites of disease associated with high morbidity. In order to establish that binding of parasite-infected red blood cells to TM is dependent on its containing chondroitin-4-sulfate (CSA), we have mutated the CSA-attachment site of murine TM, and expressed this mutant form (TMser-gly) in COS-7 cells. In cytoadhesion assays, we demonstrate that, in contrast to wild-type TM which contains CSA and supports the adhesion of 1466 PRBCs/mm2, TMser-gly does not contain CSA and adhesion of PRBCs to those cells expressing TMser-gly is entirely abrogated (200 PRBCs/mm2). These studies further confirm that the CSA of TM may play a role in the pathophysiology of malaria by providing a binding site for PRBCs.

 
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