Florian Lang

Suicide for Survival - Death of Infected Erythrocytes as a Host Mechanism to Survive Malaria

The pathogen of malaria, Plasmodium, enters erythrocytes and thus escapes recognition by the immune system. The pathogen induces oxidative stress to the host erythrocyte, which triggers eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are identified by macrophages which engulf and degrade the eryptotic cells. To the extent that infected erythrocytes undergo eryptosis prior to exit of Plasmodiaand subsequent infection of other erythrocytes, the premature eryptosis may protect against malaria. Accordingly, any therapeutical intervention accelerating suicidal death of infected erythrocytes has the potential to foster elimination of infected erythrocytes, delay the development of parasitemia and favorably influence the course of malaria. Eryptosis is stimulated by a wide variety of triggers including osmotic shock, oxidative stress, energy depletion and a wide variety of xenobiotics. Diseases associated with accelerated eryptosis include sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson’s disease. Among the known stimulators of eryptosis, paclitaxel, chlorpromazine, cyclosporine, curcumin, PGE2 and lead have indeed been shown to favourably influence the course of malaria. Moreover, sickle-cell trait, beta-thalassemia trait, glucose-6-phosphate dehydrogenase (G6PD)-deficiency and iron deficiency confer some protection against a severe course of malaria. Importantly, counteracting Plasmodia by inducing eryptosis is not expected to generate resistance of the pathogen, as the proteins involved in suicidal death of the host cell are not encoded by the pathogen and thus cannot be modified by mutations of its genes.

Kinases, Cell Volume, and the Regulation of Chloride Channels

Florian Lang Albrecht Lepple-Wienhues Ildicko Szabo Erich Gulbins^, Monica Palmada Sabine Wallisch Christoph Bohmer Karin Klingel^ and Reinhard Kandolf^ 1 2 Department of Physiology; Department of Molecular Biology, University of Essen; Department of Molecular Pathology, Eberhard-Karls-University of Tuebingen, Gmelinstrasse 5, D-72076 Tuebingen, Germany; Tel: +49 7071 29 72194; Fax: +49 7071 29 5618; e-mail: florian.lang @uni-tuebingen.de