( rotein called PfEMP-1. To evade th...)Scientists Unveil Mechanism Behind Resistance to Severe Malaria ,Health

rotein called PfEMP-1.

To evade the immune system, the malarial parasites produce proteins, including PfEMP-1, that remodel the red blood cell’s surface to their advantage. For example, when spikes of PfEMP-1 are distributed evenly over the surface of an infected AA red blood cell, they act like grappling hooks, allowing the parasitized cells to stick in tiny capillaries and avoid being cleared from the bloodstream. When parasite-infected red blood cells stick to blood vessel walls, the resulting inflammation may increase the severity of malarial symptoms, explains Dr. Wellems.

Dr. Wellems and his colleagues found uneven and reduced distribution of PfEMP-1 on the surface of parasite-infected red blood cells from children with at least one hemoglobin C gene. This abnormal distribution of PfEMP-1 significantly impairs the infected cells’ “stickiness.” For instance, laboratory-grown, parasitized AC blood cells agglutinated at a 75 percent lower rate than did AA red blood cells, while parasitized CC blood cells did not stick to each other at all. Rosette formation, in which parasitized cells attach to non-parasitized cells, also occurred significantly less often with AC and CC blood cells than with AA blood cells. Rosettes can impede blood flow in small vessels of the brain, contributing to cerebral malaria and death, notes Dr. Wellems. The scientists showed that AA cells often stick to blood vessel walls, whereas this occurs much less often with both AC and CC blood cells.

Together, the data from Dr. Wellems’ team may explain why red blood cells containing hemoglobin C are less hospitable to malaria parasites than normal AA red blood cells. For people with at least one gene for hemoglobin C, the result is less severe malaria.

Reference: RM Fairhurst et al. Abnormal PfEMP-1 display on hemoglobin C erythrocytes may protect against malaria. Nature 435:1117-21 (2005) doi:10.1038nature/03631. News releases, fact sheets and other
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