Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin.
Sickle trait, the heterozygous state of normal hemoglobin A (HbA) and sickle hemoglobin S (HbS), confers protection against malaria in Africa. AS children infected with Plasmodium falciparum are less likely than AA children to suffer the symptoms or severe manifestations of malaria, and they often carry lower parasite densities than AA children. The mechanisms by which sickle trait might confer such malaria protection remain unclear. We have compared the cytoadherence properties of parasitized AS and AA erythrocytes, because it is by these properties that parasitized erythrocytes can sequester in postcapillary microvessels of critical tissues such as the brain and cause the life-threatening complications of malaria. Our results show that the binding of parasitized AS erythrocytes to microvascular endothelial cells and blood monocytes is significantly reduced relative to the binding of parasitized AA erythrocytes. Reduced binding correlates with the altered display of P. falciparum erythrocyte membrane protein-1 (PfEMP-1), the parasite's major cytoadherence ligand and virulence factor on the erythrocyte surface. These findings identify a mechanism of protection for HbS that has features in common with that of hemoglobin C (HbC). Coinherited hemoglobin polymorphisms and naturally acquired antibodies to PfEMP-1 may influence the degree of malaria protection in AS children by further weakening cytoadherence interactions.
Cholera
Rushina
R
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Brittain
Nathaniel J
NJ
Gillrie
Mark R
MR
Lopera-Mesa
Tatiana M
TM
Diakité
Séidina A S
SA
Arie
Takayuki
T
Krause
Michael A
MA
Guindo
Aldiouma
A
Tubman
Abby
A
Fujioka
Hisashi
H
Diallo
Dapa A
DA
Doumbo
Ogobara K
OK
Ho
May
M
Wellems
Thomas E
TE
Fairhurst
Rick M
RM
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D006450:Hemoglobin SC Disease / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D006451:Hemoglobin, Sickle / Q000378:metabolism*; D006801:Humans; D008833:Microcirculation / Q000166:cytology; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000166:cytology; D010963:Plasmodium falciparum / Q000502:physiology*; D015800:Protozoan Proteins / Q000378:metabolism; D012805:Sickle Cell Trait / Q000378:metabolism / Q000469:parasitology / Q000473:pathology
D006451:Hemoglobin, Sickle; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum