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Impaired cytoadherence of Plasmodium falciparum -infected erythrocytes containing sickle hemoglobin
Open accessAbstract
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.
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“As a consequence, the balance between damaging prooxidative molecules such as free heme or iron and antioxidative factors such as carbon monoxide (CO) and bilirubin is shifted towards cytoprotection (Cholera et al., 2008;Ferreira et al., 2011;Gong et al., 2013;Jeney et al., 2014).”
From Iron in infection and immunity (2020) · cites this paper as Cholera et al., 2008
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Metadata
- Authors
- Cholera, R., Brittain, N. J., Gillrie, M. R., Lopera-Mesa, T. M., Diakité, S. A. S., Arie, T., Krause, M. A., Guindo, A., Tubman, A., Fujioka, H., Diallo, D. A., Doumbo, O. K., Ho, M., Wellems, T. E., & Fairhurst, R. M.
- Affiliations
- National Institutes of Health (US)
- University of Calgary (CA)
- Malaria Research and Training Center, Faculty of Medicine, Pharmacy, and Odontostomatology, University of Bamako, Bamako, BP 1805, Mali; and
- University of Bamako (ML)
- Case Western Reserve University (US)
- Corresponding author
- Wellems, Thomas E.
- Fairhurst, Rick M.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2008-01-22
- Volume
- 105
- Issue
- 3
- Pages
- 991-996
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2242681
- OpenAlex
- W2111913495
- Cited by
- 249
- References
- 45
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 3 · 2023: 14 · 2022: 7 · 2021: 15 · 2020: 16 · 2019: 16 · 2018: 8 · 2017: 11 · 2016: 16 · 2015: 14 · 2014: 16 · 2013: 19 · 2012: 18
- FWCI
- 19.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
- Health Sciences › Medicine › Genetics (clinical) › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Hematology › Blood groups and transfusion
- Keywords
- sickle cell trait, hemoglobin S, Plasmodium falciparum, cytoadherence, malaria prevention, PfEMP1, erythrocyte membrane protein 1, hemoglobin C, endothelial cell adhesion, monocyte adhesion, naturally acquired antibodies, hemoglobin polymorphism, children
- MeSH terms
- Animals, Cell Adhesion, Cells, Cultured, Erythrocytes, Hemoglobin SC Disease, Hemoglobin, Sickle, Humans, Microcirculation, Monocytes, Plasmodium falciparum, Sickle Cell Trait, Protozoan Proteins, Endothelial Cells, Microscopy, Electron, Transmission
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