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Platelet-endothelial cell interactions in cerebral malaria: The end of a cordial understanding

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
Topic:

Infections of the Endothelium

DOI: http://dx.doi.org/10.1160/TH09-05-0337
Issue: 2009: 102/6 (Dec) pp. 1007–1291
Pages: 1093-1102

Platelet-endothelial cell interactions in cerebral malaria: The end of a cordial understanding

Dorothée Faille1- 3; Fatima El-Assaad 1; Marie-Christine Alessi 3; Thierry Fusai 2; Valéry Combes 1; Georges E. Grau1

1Department of Pathology, University of Sydney, Camperdown, New South Wales, Australia; 2 Unité de Recherche en Biologie et Epidémiologie Parasitaires, Institut de Médecine Tropicale du Service de Santé des Armées, Marseille, France; 3 Inserm U626, Aix-Marseille Université, Faculté de Médecine, Marseille, France

Keywords

infectious diseases, Platelet immunology, endothelial cells, microparticles

Summary

Cerebral malaria is an acute encephalopathy evolving from an infection with Plasmodium falciparum which kills more than one million people each year. Brain tissues from patients who died with cerebral malaria revealed multifocal capillary obstruction by parasitised red blood cells, platelets, and leukocytes. Many studies are unified in their proposal of two major hypotheses consisting of cell adhesion to the brain endothelium and excessive immune stimulation resulting in further vascular inflammation, prothrombotic cell activation, mechanical obstruction of cerebral capillaries and, consequently, blood-brain barrier disruption. Platelets and endothelial cells communicate on multiple levels. Infection-induced changes in platelets and endothelial cells occur in cerebral malaria, resulting in their concomitant activation, increased interactions between these two cell types, and a secondary procoagulant or hypercoagulable state. Here we review evidence for these mechanisms and highlight the possible role of platelets as effectors of endothelial damage in cerebral malaria. A better understanding of the complex regulation of these various interactions between brain endothelial cells and platelets in the context of cerebral malaria may prove useful in the development of new approaches to the treatment of this disease.

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