Accelerated clearance of Plasmodium-infected erythrocytes in sickle cell trait and annexin-A7 deficiency.

Abstract

The course of malaria does not only depend on the virulence of the parasite Plasmodium but also on properties of host erythrocytes. Here, we show that infection of erythrocytes from human sickle cell trait (HbA/S) carriers with ring stages of P. falciparum led to significantly enhanced PGE(2) formation, Ca(2+) permeability, annexin-A7 degradation, phosphatidylserine (PS) exposure at the cell surface, and clearance by macrophages. P. berghei-infected erythrocytes from annexin-A7-deficient (annexin-A7(-/-)) mice were more rapidly cleared than infected wildtype cells. Accordingly, P. berghei-infected annexin-A7(-/-) mice developed less parasitemia than wildtype mice. The cyclooxygenase inhibitor aspirin decreased erythrocyte PS exposure in infected annexin-A7(-/-) mice and abolished the differences of parasitemia and survival between the genotypes. Conversely, the PGE(2)-agonist sulprostone decreased parasitemia and increased survival of wild type mice. In conclusion, PS exposure on erythrocytes results in accelerated clearance of Plasmodium ring stage-infected HbA/S or annexin-A7(-/-) erythrocytes and thus confers partial protection against malaria in vivo.

• Authors: Philipp A Lang, Ravi S Kasinathan, Verena B Brand, Christophe Duranton, Camelia Lang, Saisudha Koka, Ekaterina Shumilina, Daniela S Kempe, Valerie Tanneur, Ahmad Akel, Karl S Lang, Michael Foller, Jurgen F J Kun, Peter G Kremsner, Sebastian Wesselborg, Stefan Laufer, Christoph S Clemen, Claudia Herr, Angelika A Noegel, Thomas Wieder, Erich Gulbins, Florian Lang, Stephan M Huber
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 24 Issue 5-6 Pg. 415-28 ( 2009) ISSN: 1421-9778 [Electronic] Germany
• PMID: 19910682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2009 S. Karger AG, Basel.

Chemical References

• Annexin A7
• Hemoglobin, Sickle
• Phosphatidylserines
• sulprostone
• Hemoglobin A
• Dinoprostone
• Aspirin
• Calcium

Topics

• Animals
• Annexin A7 (deficiency, genetics, metabolism)
• Aspirin (therapeutic use)
• Calcium (metabolism)
• Dinoprostone (analogs & derivatives, metabolism, therapeutic use)
• Erythrocytes (metabolism, parasitology)
• Genotype
• Hemoglobin A (metabolism)
• Hemoglobin, Sickle (metabolism)
• Humans
• Mice
• Mice, Knockout
• Parasitemia (drug therapy)
• Phagocytosis
• Phosphatidylserines (metabolism)
• Plasmodium berghei (growth & development, physiology)
• Plasmodium falciparum (growth & development, physiology)
• Sickle Cell Trait (metabolism, parasitology)