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- Title
Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria.
- Authors
Fairhurst, Rick M.; Baruch, Dror I.; Brittain, Nathaniel J.; Ostera, Graciela R.; Wallach, John S.; Hoang, Holly L.; Hayton, Karen; Guindo, Aldiouma; Makobongo, Morris O.; Schwartz, Owen M.; Tounkara, Anatole; Doumbo, Ogobara K.; Diallo, Dapa A.; Fujioka, Hisashi; Ho, May; Wellems, Thomas E.
- Abstract
Haemoglobin C, which carries a glutamate-to-lysine mutation in the β-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.
- Subjects
WEST Africa; MALARIA; PLASMODIUM falciparum; ERYTHROCYTES; HEMOGLOBINS; BLOOD plasma; CELL membranes; CELL adhesion molecules
- Publication
Nature, 2005, Vol 435, Issue 7045, p1117
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature03631