Effect of cyclosporine on parasitemia and survival of Plasmodium berghei infected mice.
Cyclosporine triggers suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. The present study explored whether cyclosporine influences eryptosis of Plasmodium infected erythrocytes, development of parasitemia and thus the course of the disease. Annexin V binding was utilized to depict phosphatidylserine exposure and forward scatter in FACS analysis to estimate erythrocyte volume. In vitro infection of human erythrocytes with Plasmodium falciparum increased annexin binding and decreased forward scatter, effects potentiated by cyclosporine (> or = 0.01 microM). Cyclosporine (> or = 0.001 microM) significantly decreased intraerythrocytic DNA/RNA content and in vitro parasitemia (> or = 0.01 microM). Administration of cyclosporine (5 mg/kg b.w.) subcutaneously significantly decreased the parasitemia (from 47% to 27% of circulating erythrocytes 20 days after infection) and increased the survival of P. berghei infected mice (from 0% to 94% 30 days after infection). In conclusion, cyclosporine augments eryptosis, decreases parasitemia and enhances host survival during malaria.
Bobbala
Diwakar
D
Physiologisches Institut, der Universität Tübingen, Gmelinstr. 5, D-72076 Tübingen, Germany.
Koka
Saisudha
S
Lang
Camelia
C
Boini
Krishna M
KM
Huber
Stephan M
SM
Lang
Florian
F
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000469:parasitology*; D051379:Mice; D008815:Mice, Inbred Strains; D018512:Parasitemia / Q000469:parasitology*; D010718:Phosphatidylserines / Q000378:metabolism; D010962:Plasmodium berghei / Q000187:drug effects* / Q000502:physiology
D010718:Phosphatidylserines; D016572:Cyclosporine