Unité de Parasitologie Expérimentale, EA 3282, IFR 48, Faculties of Medicine and Pharmacy, Université de la Méditerranée, F-13 385 Marseille Cedex 05, France
Address for correspondence: Dr. Georges E. Unité de Parasitologie Expérimentale, EA 3282, IFR 48, Faculties of Medicine and Pharmacy, Université de la Méditerranée, 27, Boulevard Jean Moulin, F-13 385 Marseille Cedex 05, Francee. Voice: +33-4-91 32 46 48; fax: + 33-4-91 32 46 34.
georges.grau{at}medecine.univ-mrs.fr
Ann. N.Y. Acad. Sci. 992: 30-38 (2003).
Cerebral malaria (CM), one of the most serious complications
of
Plasmodium falciparum infection, is characterized by the
sequestration of infected erythrocytes (IEs) in cerebral microvascular
beds. The precise mechanisms involved in the onset of neuropathology
remain unknown, but parasite sequestration in the brain, metabolic
disturbances, and host immune responses all play a role. Studies
in a murine model of CM showed a potential role for host cells,
especially platelets, in the pathogenesis of CM. Indeed, urokinase
plasminogen activator receptor (uPAR; CD87) deficiency attenuates
the severity of CM, most likely by its important role in platelet
kinetics and trapping. These results led us to evaluate whether
platelets have a role in the human disease. By immunostaining
of brain samples from Malawian patients, we determined that
the surface of platelet accumulation and the proportion of vessels
filled with platelets were significantly higher in patients
who died of CM than in those who died of other causes. We then
investigated the role of platelets in IE cytoadhesion
in vitro,
using CD36-binding IE (IECD36) and CD36-deficient (CD36DEF)
brain microvascular endothelial cells (ECs). Coincubation studies
indicated that platelets can induce strong IECD36 binding to
CD36DEF ECs and, conversely, can hide constitutively expressed
falciparum receptors such as chondroitin sulfate A. Thus, platelets
may provide an adhesion receptor to microvascular beds originally
devoid of it. This novel mechanism of cytoadhesion may reorient
the sequestration of different parasite phenotypes and play
an important role in the pathogenesis of severe malaria.
