Journal Article

Impaired cytoadherence of Plasmodium falciparum-infected erythrocytes containing sickle hemoglobin

Brittain, Nathaniel J, Tubman, Abby, Lopera-Mesa, Tatiana M, Diakité, Séidina A.S, Krause, Michael A, Cholera, Rushina, Ho, May, Arie, Takayuki, Gillrie, Mark R, Wellems, Thomas E, Guindo, Aldiouma, Fairhurst, Rick M, Diallo, Dapa A, Fujioka, Hisashi, Doumbo, Ogobara K

2008

Overview

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.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: abnormal hemoglobin / Africa / Animals / antibodies / Biological Sciences / Biological variation / Blood / brain / Cell Adhesion / Cells / Cells, Cultured / Children / endothelial cells / Endothelial Cells - cytology / Erythrocytes / Erythrocytes - cytology / Erythrocytes - metabolism / Erythrocytes - ultrastructure / Hemoglobin / Hemoglobin SC Disease - metabolism / Hemoglobin SC Disease - parasitology / Hemoglobin SC Disease - pathology / Hemoglobin, Sickle - metabolism / Hemoglobins / heterozygosity / Humans / Macrophages / Malaria / Microcirculation - cytology / Microscopy, Electron, Transmission / Monocytes / Monocytes - cytology / Parasites / Parasitism / Plasmodium falciparum / Plasmodium falciparum - physiology / Polymorphism / Protozoan Proteins - metabolism / Sickle Cell Trait - metabolism / Sickle Cell Trait - parasitology / Sickle Cell Trait - pathology / Sickles / tissues / Vector-borne diseases / Virology / virulence