Accelerated clearance of Plasmodium-infected erythrocytes in sickle cell trait and annexin-A7 deficiency.
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.
Lang
Philipp A
PA
Department of Physiology, University of Tübingen, Germany.
Kasinathan
Ravi S
RS
Brand
Verena B
VB
Duranton
Christophe
C
Lang
Camelia
C
Koka
Saisudha
S
Shumilina
Ekaterina
E
Kempe
Daniela S
DS
Tanneur
Valerie
V
Akel
Ahmad
A
Lang
Karl S
KS
Foller
Michael
M
Kun
Jurgen F J
JF
Kremsner
Peter G
PG
Wesselborg
Sebastian
S
Laufer
Stefan
S
Clemen
Christoph S
CS
Herr
Claudia
C
Noegel
Angelika A
AA
Wieder
Thomas
T
Gulbins
Erich
E
Lang
Florian
F
Huber
Stephan M
SM
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*
D017310:Annexin A7; D006451:Hemoglobin, Sickle; D010718:Phosphatidylserines; C016767:sulprostone; D006441:Hemoglobin A; D015232:Dinoprostone; D001241:Aspirin; D002118:Calcium