Suicidal erythrocyte death or eryptosis is characterized by erythrocyte shrinkage, cell membrane blebbing, and cell membrane scrambling with
phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca(2+) entry,
ceramide formation, stimulation of
caspases,
calpain activation, energy depletion, oxidative stress, and dysregulation of several
kinases. Eryptosis is triggered by a wide variety of
xenobiotics. It is inhibited by several
xenobiotics and endogenous molecules including NO and
erythropoietin. The susceptibility of erythrocytes to eryptosis increases with erythrocyte age.
Phosphatidylserine exposing erythrocytes adhere to the vascular wall by binding to endothelial CXC-Motiv-Chemokin-16/
Scavenger-receptor for
phosphatidylserine and
oxidized low density lipoprotein (CXCL16).
Phosphatidylserine exposing erythrocytes are further engulfed by phagocytosing cells and are thus rapidly cleared from circulating blood. Eryptosis eliminates infected or defective erythrocytes thus counteracting
parasitemia in
malaria and preventing detrimental
hemolysis of defective cells. Excessive eryptosis, however, may lead to
anemia and may interfere with microcirculation. Enhanced eryptosis contributes to the pathophysiology of several clinical disorders including
metabolic syndrome and diabetes,
malignancy, cardiac and
renal insufficiency,
hemolytic uremic syndrome,
sepsis,
mycoplasma infection,
malaria,
iron deficiency,
sickle cell anemia,
thalassemia,
glucose 6-phosphate
dehydrogenase deficiency, and
Wilson's disease. Facilitating or inhibiting eryptosis may be a therapeutic option in those disorders.