| Summary: | <p>Platelet-mediated clumping of <em>Plasmodium falciparum</em>-infected erythrocytes (IEs) is a common property of field isolates associated with severe disease (Pain, Ferguson <em>et al</em>. 2001). Platelet receptors CD36 (Pain, Ferguson <em>et al</em>. 2001), P-Selectin (Wassmer, Taylor <em>et al</em>. 2008) and gC1qR (Biswas, Hafiz <em>et al</em>. 2007) mediate clumping. To characterize the molecular specificities of the clumping phenotype, I cloned clumping parasite line IT/C10 by limiting dilution. I characterized <em>var</em> gene expression in the IT/C10 clones using generic primers for the DBL tag region (Bull, Berriman <em>et al</em>. 2005). Clumping assays were conducted in the presence of specific reagents to delineate host factors hypothesized to contribute to development of the clumping phenotype. Finally, I conducted a clinical study with isolates from children with malaria in Kilifi, Kenya.</p> <p>This study shows that in parasite line IT/C10, platelet-mediated clumping is associated with Itvar30 suggesting a prominent role for the PfEMP-1 encoded by this <em>var</em> gene in development of platelet-mediated clumping. For IT/C10 parasites, platelet activation appears to be involved in platelet-mediated clumping. Platelet P-Selectin appears to mediate clumping using lectin-dependent interactions. To further elucidate the mechanisms that mediate clumping by host platelets, I have used a panel of platelet antagonists to delineate specific platelet activation pathways. Our results show that platelet activation plays an important role in platelet-mediated clumping. Finally, in this study, platelet-mediated clumping was associated with parasitaemia, but not with disease severity.</p>
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