Abstract
Neocytolysis is the hypothesis formulated to explain experimental evidence of selective lysis of young red blood cells (RBCs) (neocytes) associated with decreased plasma levels of erythropoietin (EPO). In humans, it appears to take place whenever a fast RBC mass reduction is required, i.e., in astronauts during the first days of spaceflight under weightlessness, where a fast reduction in plasma volume and increase in haematocrit occur. EPO plasma levels then decline and a decrease in RBC mass takes place, apparently because of the selective lysis of the youngest, recently generated RBCs (neocytes). The same process seems to occur in people descending to sea level after acclimatization at high altitude. After descent, the polycythaemia developed at high altitude must be abrogated, and a rapid reduction in the number of circulating RBCs is obtained by a decrease in EPO synthesis and the lysis of what seem to be young RBCs. In vivo, neocytolysis seems to be abolished by EPO administration. More recent research has ascribed to neocytolysis the RBC destruction that occurs under such disparate pathophysiologic conditions as nephropathy, severe obstructive pulmonary disease, blood doping, and even malaria anaemia. According to the theory, EPO's central role would be not only to stimulate the production of new RBCs in conditions of anaemia, as maintained by the orthodox view, but also that of a cytoprotective factor for circulating young RBCs. Why neocytes are specifically destroyed and how is this related to decreased EPO levels has not yet been elucidated. Changes in membrane molecules of young RBCs isolated from astronauts or mountain climbers upon return to normal conditions seem to indicate a higher susceptibility of neocytes to ingestion by macrophages. By limiting the context to space missions and high altitude expeditions, this review will address unresolved and critical issues that in our opinion have not been sufficiently highlighted in previous works.
Highlights
The red blood cells (RBCs) of mammals are non-nucleated cells that spend in the circulation a limited amount of time, after which they are removed by the reticulo-endothelial system according to a species-specific type of kinetic
Mechanisms for the selective removal of RBCs produced under conditions of acutely enhanced erythropoiesis may www.frontiersin.org be invoked (Landaw, 1988) but this explanation, while possibly applicable to RBCs produced at high altitude under hypoxic conditions, does not obviously work for space anaemia, where neocytes that were produced before flight are supposed to be destroyed
The factors determining the lifespan of cells that circulate in blood are not fully understood
Summary
The red blood cells (RBCs) of mammals are non-nucleated cells that spend in the circulation a limited amount of time, after which they are removed by the reticulo-endothelial system according to a species-specific type of kinetic This results from the superimposition of random destruction (independent of cell age) and of a senescence process. The magnitude of the random component varies in different species and in different animals within the same species It is very pronounced in mice and rats, less pronounced in pigs, rabbits and other mammalians, and almost absent in normal human RBCs, which are recognized as senescent and removed after 120 days of circulatory life (Clark, 1988; Landaw, 1988; Brovelli and Minetti, 2003). It is an accepted view that, under physiologic conditions, no mechanisms exist (or are not known), which are able to decrease the RBC life-span below an established, fixed value, which, in humans, amounts to the said 120 days (corresponding to the removal of approximately 1% RBCs per day)
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