The negative regulation of red cell mass by neocytolysis: Physiologic and pathophysiologic manifestations

Lawrence Rice, Clarence P. Alfrey

Research output: Contribution to journalReview articlepeer-review

146 Scopus citations


We have uncovered a physiologic process which negatively regulates the red cell mass by selectively hemolyzing young circulating red blood cells. This allows fine control of the number of circulating red blood cells under steady-state conditions and relatively rapid adaptation to new environments. Neocytolysis is initiated by a fall in erythropoietin levels, so this hormone remains the major regulator of red cell mass both with anemia and with red cell excess. Physiologic situations in which there is increased neocytolysis include the emergence of newborns from the hypoxic uterine environment and the descent of polycythemic high-altitude dwellers to sea level. The process first became apparent while investigating the mechanism of the anemia that invariably occurs after spaceflight. Astronauts experience acute central plethora on entering microgravity resulting in erythropoietin suppression and neocytolysis, but the reduced blood volume and red cell mass become suddenly maladaptive on reentry to earth's gravity. The pathologic erythropoietin deficiency of renal disease precipitates neocytolysis, which explains the prolongation of red cell survival consistently resulting from erythropoietin therapy and points to optimally efficient erythropoietin dosing schedules. Implications should extend to a number of other physiologic and pathologic situations including polycythemias, hemolytic anemias, "blood-doping" by elite athletes, and oxygen therapy. It is likely that erythropoietin influences endothelial cells which in turn signal reticuloendothelial phagocytes to destroy or permit the survival of young red cells marked by surface molecules. Ongoing studies to identify the molecular targets and cytokine intermediaries should facilitate detection, dissection and eventual therapeutic manipulation of the process.

Original languageEnglish (US)
Pages (from-to)245-250
Number of pages6
JournalCellular Physiology and Biochemistry
Issue number6
StatePublished - 2005


  • Blood Doping
  • Erythropoiesis
  • Erythropoietin
  • Hemolytic Anemia
  • Neocytolysis
  • Polycythemia
  • Red Cell Mass
  • Spaceflight Anemia

ASJC Scopus subject areas

  • Physiology
  • Cell Biology


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