title: 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.affiliation: Department of Physiology, University of Tübingen, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Lang
authors.forename: Ravi S
authors.initials: RS
authors.lastname: Kasinathan
authors.forename: Verena B
authors.initials: VB
authors.lastname: Brand
authors.forename: Christophe
authors.initials: C
authors.lastname: Duranton
authors.forename: Camelia
authors.initials: C
authors.lastname: Lang
authors.forename: Saisudha
authors.initials: S
authors.lastname: Koka
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Shumilina
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Kempe
authors.forename: Valerie
authors.initials: V
authors.lastname: Tanneur
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akel
authors.forename: Karl S
authors.initials: KS
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Foller
authors.forename: Jurgen F J
authors.initials: JF
authors.lastname: Kun
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Sebastian
authors.initials: S
authors.lastname: Wesselborg
authors.forename: Stefan
authors.initials: S
authors.lastname: Laufer
authors.forename: Christoph S
authors.initials: CS
authors.lastname: Clemen
authors.forename: Claudia
authors.initials: C
authors.lastname: Herr
authors.forename: Angelika A
authors.initials: AA
authors.lastname: Noegel
authors.forename: Thomas
authors.initials: T
authors.lastname: Wieder
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Huber
mesh_terms: D000818:Animals; D017310:Annexin A7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D001241:Aspirin / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology; D005838:Genotype; D006441:Hemoglobin A / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018512:Parasitemia / Q000188:drug therapy; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism; D010962:Plasmodium berghei / Q000254:growth & development / Q000502:physiology; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D012805:Sickle Cell Trait / Q000378:metabolism / Q000469:parasitology*
chemical_list: D017310:Annexin A7; D006451:Hemoglobin, Sickle; D010718:Phosphatidylserines; C016767:sulprostone; D006441:Hemoglobin A; D015232:Dinoprostone; D001241:Aspirin; D002118:Calcium