Editorial board editor-in-chief

Eryptosis – death program of erythrocytes
The erythrocyte rigorously obeys imposed rules within the rela-
tively narrow range of freedom. As a matter of fact the erythrocyte 
could be viewed as a biological robot which may not necessarily 
be alive. However, its determined life span is a feature of liv
-
ing systems. The relatively abrupt limit to life, which is species 
speciic, indicates that erythrocyte death is not a simple result 
of more and more injuries, but of taking into account the internal 
clock and death mechanism in its program (Fig. 4).

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27
System biolog
y
The criteria of life and aging from a molecular viewpoint…
channel) and leads to potassium loss. In order to differentiate 
this process from apoptosis in nucleated cells, it is referred to as 
eryptosis. Evidence shows that prostaglandins are also involved 
in the regulation of erythrocyte death [22]. Phosphatidylserine in 
the external layer of the cell membrane (being also the feature of 
nucleated cells undergoing apoptosis) is recognised by macro-
phages [23]. It is a result of limiting the quantity of ATP available 
to ATP-dependent lippase, the protein which is responsible for 
transport of this phospholipid to the internal cell membrane. Ad
-
ditionally, abrupt increase in the concentration of calcium ions 
during eryptosis leads to activation of scramblase, an enzymatic 
protein necessary for phosphatidylserine externalization [24]. All 
these changes enable phagocytes to recognize aging erythro-
cytes. The above described processes lead to removal of red 
blood cells from the vascular lumen.
Programmed erythrocyte death allows for control. The 
breakdown of red blood cells is extravascular and occurs in the 
monocyte-macrophage system of the spleen, the liver and the 
bone marrow. Intravascular hemolysis is unfavorable and it may 
occur in the course of hemolytic diseases, for instance transfusion 
of incompatible blood in the AB0 or Rh system or in the course 
of a rare disease paroxysmal nocturnal hemoglobinuria [11]. 
Therefore, the programmed alteration in cell surface structure 
is the body’s strategy enabling the phagocytes to recognize 
such blood cells. 
Erythrocyte life span is also dependent on osmotic and oxi-
dative stress. Death of erythrocytes is a complex programmed 
metabolic process. Only 0.06-0.4% of red blood cells, irrespective 
of their age, are destroyed accidentally, in a non-programmed 
manner [11]. Interestingly, erythropoietin has been found to 
increase erythrocyte life span. The protective effects of erythro
-
poietin are observed in dialysis patients when the number of cells 
exposing phosphatedylserine (which is a signal for cell removal) 
decreases several hours after hormone injection. It appears then 
that in exceptional cases the programmed erythrocyte life span 
can be modiied by a signal command [12, 25].
According to the approved criteria erythrocytes, unlike vi-
ruses, are living things. They are automatons with a naturally 
determined life span.