As intraerythrocytic parasites develop they dramatically increase the viscosity of the Parasitized Blood Cell (PRBC) as fluid-like hemoglobin is replaced with the complex intracellular structures usually associated with typical eukaryotic cells. Viscous parasite packed PRBCs are targeted for mechanical clearance as they attempt to pass through the 2μm gaps of the sieve-like red pulp of the mammalian spleen. It has been suggested that increases in Plasmodium vivax PRBC membrane deformability may allow it to avoid splenic clearance. This hypothesis was tested by applying freshly isolated P. vivax to a microfluidic chamber with a 2μm constriction. This ex vivo splenic clearance model was also used to examine the rheological behavior of P. falciparum PRBCs and Unparasitized Red Blood Cells (URBCs) under flow. Unlike P. falciparum, all developmental stages of P. vivax were able to deform and transverse the 2μm constriction. The transit velocity of P.vivax PRBCs through this gap did not significantly decrease as the parasite matured. The recovery of constricted erythrocytes is not affected by P.vivax, an observation unique in the suborder Haemosporina. Interestingly ~15% of URBCs from P. vivax patients were destroyed by the constriction, suggesting that parasite derived molecules or host immunointermediaries may be responsible for erythrocyte membrane damage. Anemia induced through the destruction of URBCs and the subsequent increase in reticulocyte production (the sole invasion target for P. vivax), allows this species to achieve a level of fitness not possible due to the normally low reticulocyte count.
|Date of Award||Dec 2008|
|Supervisor||Nicholas Anstey (Supervisor)|