Erythrocyte remodeling by malaria parasites

PURPOSE OF REVIEW: Plasmodium falciparum causes the most virulent form of human malarias. It is a protozoan parasite that infects human erythrocytes and the erythrocytic stages are responsible for all symptoms and pathologies of the disease. Critical to infection is the formation of a parasitophorous vacuolar membrane at the time of entry and within which the intracellular parasite proliferates. Since erythrocytes lack endocytic machinery, it is surprising that they can be infected by pathogens. This review summarizes recent studies of the erythrocyte-malaria interaction that have provided insights into properties of erythrocyte membranes as well as parasite mechanisms that remodel the erythrocyte. RECENT FINDINGS: Themes revealed by recent literature suggest that both parasite and erythrocyte components regulate parasite entry and intracellular growth by extensively remodeling host membranes. These remodeling events include the invagination of the host cell membrane during parasite entry that results in the creation and maintenance of a vacuole that surrounds the intracellular organism, and the development of antigenic, structural and transport alterations during intracellular parasite development. SUMMARY: The implications are that malarial erythrocyte remodeling events occur at a significant cost to the human host since many of the associated virulence events have been linked to severe disease pathologies.     

Association between morphologic distortion of sickle cells and deoxygenation-induced cation permeability increase

We hypothesized that the deoxygenation-induced increase in cation permeability of sickle cells was related to mechanical distention of the membrane by growing HbS polymer within the cell. To test this hypothesis, we determined the effect of deoxygenation on cation fluxes in sickle cells under conditions that restricted or permitted extensive growth of polymer, producing different degrees of membrane distention. Manipulation of suspending medium osmolality for density-isolated high and low mean cell hemoglobin concentration (MCHC) cells was used to regulate the extensional growth of polymer bundles and hence membrane distortion. For initially low MCHC cells, the deoxygenation-induced increase in both Na and K fluxes was markedly suppressed when the MCHC was increased by increasing the osmolality. This suppression corresponded to the inhibition of extensive morphologic cellular distortion. For initially high MCHC, ISC-rich cells, deoxygenation had minimal effect on K permeability. However, reduction of MCHC by a decrease in osmolality produced a concomitant increase in cation permeability and cellular distortion. These observations support the idea that the sickling-associated increase in membrane permeability is related to mechanical stress imposed on the membrane by bundles of HbS polymer.