Channel-induced apoptosis of infected host cells-the case of malaria.
Infection of erythrocytes by the malaria pathogen Plasmodium falciparum leads to activation of several distinct anion channels and a non-selective, Ca2+-permeable cation channel. All channel types are presumably activated by the oxidative stress generated by the pathogen. Similar or identical channels are activated by oxidation of non-infected erythrocytes. Activation of the non-selective cation channel allows entry of Ca2+ and Na+, both of which are required for intracellular growth of the pathogen. The entry of Ca2+ stimulates an intraerythrocytic scramblase that facilitates bi-directional phospholipid migration across the bilayer, resulting in breakdown of the phosphatidylserine asymmetry of the cell membrane. The exposure of phosphatidylserine at the outer surface of the cell membrane is presumably followed by binding to phosphatidylserine receptors on macrophages and subsequent phagocytosis of the affected erythrocyte. The lysosomal degradation may eventually eliminate the pathogen. The channel may thus play a dual role in pathogen survival. Absence of the channels is not compatible with pathogen growth, enhanced channel activity accelerates erythrocyte "apoptosis" that may represent a host defence mechanism serving to eliminate infected erythrocytes.
Lang
Florian
F
Physiologisches Institut der Universität Tübingen, Gmelinstrasse 5, 72076 Tübingen, Germany. florian.lang@uni-tuebingen.de
Lang
Philipp A
PA
Lang
Karl S
KS
Brand
Verena
V
Tanneur
Valerie
V
Duranton
Christophe
C
Wieder
Thomas
T
Huber
Stephan M
SM
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology*; D004910:Erythrocyte Membrane / Q000378:metabolism / Q000469:parasitology; D004912:Erythrocytes / Q000469:parasitology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D016778:Malaria, Falciparum / Q000503:physiopathology*; D008564:Membrane Potentials / Q000502:physiology; D010963:Plasmodium falciparum
D015220:Calcium Channels; D007473:Ion Channels; C505335:surface anion channel protein, Plasmodium falciparum