Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria - PubMed (original) (raw)

. 2005 Jun 23;435(7045):1117-21.

doi: 10.1038/nature03631.

Dror I Baruch, Nathaniel J Brittain, Graciela R Ostera, John S Wallach, Holly L Hoang, Karen Hayton, Aldiouma Guindo, Morris O Makobongo, Owen M Schwartz, Anatole Tounkara, Ogobara K Doumbo, Dapa A Diallo, Hisashi Fujioka, May Ho, Thomas E Wellems

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Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria

Rick M Fairhurst et al. Nature. 2005.

Abstract

Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria. Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature.

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