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Neocytolysis: none, one or many? A reappraisal and future perspectives.

Risso A, Ciana A, Achilli C, Antonutto G, Minetti G - Front Physiol (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural and Environmental Sciences, University of Udine Udine, Italy.

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.

No MeSH data available.


Related in: MedlinePlus

Representation of central blood pooling in space. Upon transition from normogravity (A) to microgravity (B) the blood of the peripheral vascular space shifts to central space, causing central acute plethora, accompanied by peripheral vessel constriction. An adjustment is obtained by reduction of PV and RBC mass through erythrolysis and EPO reduction (C) over the first days of spaceflight. Then, upon return to normogravity (D), the normal redistribution of blood volume and the augmentation of blood fluid reduce the haematocrit (space anemia). From Charles et al. (1994).
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Figure 1: Representation of central blood pooling in space. Upon transition from normogravity (A) to microgravity (B) the blood of the peripheral vascular space shifts to central space, causing central acute plethora, accompanied by peripheral vessel constriction. An adjustment is obtained by reduction of PV and RBC mass through erythrolysis and EPO reduction (C) over the first days of spaceflight. Then, upon return to normogravity (D), the normal redistribution of blood volume and the augmentation of blood fluid reduce the haematocrit (space anemia). From Charles et al. (1994).

Mentions: The term “neocytes” has been adopted again, more recently and in an entirely different context, with the theory proposed by Alfrey and co-workers to explain the anaemic condition that affects astronauts after space flights (“space anaemia”) (Alfrey et al., 1997). In 1965, a study showed that in astronauts participating in orbital flights Gemini IV, V, and VII, a decrease in erythrocyte survival and in RBCM was occurring, due to erythrolysis of unknown cause (Fischer et al., 1967). On escaping the Earth's gravitational force the human organism experiences a reduction in total blood volume, plasma volume (PV) and, most importantly, of RBCM. The peripheral blood normally held in place by gravity, moves to central organs where a condition of acute plethora ensues. At the same time, a 20% reduction in PV takes place by redistribution in various compartments, thus inducing an increase in haematocrit (“pseudopolycythaemia”) (Watenpaugh, 2001; De Santo et al., 2005). In the following days, a drop in EPO levels is observed, along with a decrease in RBCM of 10–15%, that has been likened to a phlebotomy of 700 ml of blood (Figure 1). According to the neocytolysis hypothesis, the latter decrease occurs too rapidly to be only the result of combined suppression of erythropoiesis and continued, normal destruction of physiologically aged RBCs (occurring at a rate of less than 1% per day), but could be explained by the selective lysis of relatively young RBCs, the “neocytes.”


Neocytolysis: none, one or many? A reappraisal and future perspectives.

Risso A, Ciana A, Achilli C, Antonutto G, Minetti G - Front Physiol (2014)

Representation of central blood pooling in space. Upon transition from normogravity (A) to microgravity (B) the blood of the peripheral vascular space shifts to central space, causing central acute plethora, accompanied by peripheral vessel constriction. An adjustment is obtained by reduction of PV and RBC mass through erythrolysis and EPO reduction (C) over the first days of spaceflight. Then, upon return to normogravity (D), the normal redistribution of blood volume and the augmentation of blood fluid reduce the haematocrit (space anemia). From Charles et al. (1994).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3924315&req=5

Figure 1: Representation of central blood pooling in space. Upon transition from normogravity (A) to microgravity (B) the blood of the peripheral vascular space shifts to central space, causing central acute plethora, accompanied by peripheral vessel constriction. An adjustment is obtained by reduction of PV and RBC mass through erythrolysis and EPO reduction (C) over the first days of spaceflight. Then, upon return to normogravity (D), the normal redistribution of blood volume and the augmentation of blood fluid reduce the haematocrit (space anemia). From Charles et al. (1994).
Mentions: The term “neocytes” has been adopted again, more recently and in an entirely different context, with the theory proposed by Alfrey and co-workers to explain the anaemic condition that affects astronauts after space flights (“space anaemia”) (Alfrey et al., 1997). In 1965, a study showed that in astronauts participating in orbital flights Gemini IV, V, and VII, a decrease in erythrocyte survival and in RBCM was occurring, due to erythrolysis of unknown cause (Fischer et al., 1967). On escaping the Earth's gravitational force the human organism experiences a reduction in total blood volume, plasma volume (PV) and, most importantly, of RBCM. The peripheral blood normally held in place by gravity, moves to central organs where a condition of acute plethora ensues. At the same time, a 20% reduction in PV takes place by redistribution in various compartments, thus inducing an increase in haematocrit (“pseudopolycythaemia”) (Watenpaugh, 2001; De Santo et al., 2005). In the following days, a drop in EPO levels is observed, along with a decrease in RBCM of 10–15%, that has been likened to a phlebotomy of 700 ml of blood (Figure 1). According to the neocytolysis hypothesis, the latter decrease occurs too rapidly to be only the result of combined suppression of erythropoiesis and continued, normal destruction of physiologically aged RBCs (occurring at a rate of less than 1% per day), but could be explained by the selective lysis of relatively young RBCs, the “neocytes.”

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Agricultural and Environmental Sciences, University of Udine Udine, Italy.

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.

No MeSH data available.


Related in: MedlinePlus