Eryptosis, the suicidal death of erythrocytes, is characterized by exposure of phosphatidylserine at the erythrocyte surface and cell shrinkage. Triggers of eryptosis include anandamide. Enhanced eryptosis of infected human erythrocytes is expected to delay the development of parasitaemia during infection with Plasmodium, the parasite causing malaria. The present experiments aimed to test, whether anandamide influences eryptosis, parasite growth and/or host survival during in vitro or in vivo infection with Plasmodia. Human erythrocytes were infected in vitro with P. falciparum, and mice in vivo with P. berghei. Parasitemia was determined with Syto16. Phosphatidylserine-exposing erythrocytes were identified by analysing annexin V-binding in FACS analysis. In vitro infection of human erythrocytes was followed by a significant increase in annexin V-binding, an effect slightly enhanced by anandamide (> or = 50 microM), which significantly reduced intraerythrocytic DNA/RNA content and in vitro parasitaemia. In vivo administration of anandamide (5 mg/kg b.w. subcutaneously) blunted the parasitaemia (from 36.9% to 24.2% of circulating erythrocytes 21 days after infection) and significantly enhanced the survival of P. berghei-infected mice (from 0% to 67% 26 days after infection). The percentage of phosphatidylserine-exposing erythrocytes was significantly increased in anandamide-treated infected mice compared to non-treated infected mice. In conclusion, anandamide stimulated eryptosis of infected erythrocytes thus counteracting parasitaemia and a lethal course of the disease.
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