Erythropoietin withdrawal alters interactions between young red blood cells, splenic endothelial cells, and macrophages: an in vitro model of neocytolysis.
BACKGROUND
We have described the rapid destruction of young red blood cells (neocytolysis) in astronauts adapting to microgravity, in polycythemic high altitude dwellers who descend to sea level, and in patients with kidney disorders. This destruction results from a decrease in erythropoietin (EPO) production. We hypothesized that such EPO withdrawal could trigger physiological changes in cells other than red cell precursors and possibly lead to the uptake and destruction of young red cells by altering endothelial cell-macrophage interactions, most likely occurring in the spleen.


METHODS
We identified EPO receptors on human splenic endothelial cells (HSEC) and investigated the responses of these cells to EPO withdrawal.


RESULTS
A monolayer of HSEC, unlike human endothelial cells from aorta, glomerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When HSEC were cultured with monocyte-derived macrophages (but not when either cell type was cultured alone), EPO withdrawal induced an increased ingestion of young red cells by macrophages when compared with the constant presence or absence of EPO.


CONCLUSIONS
HSEC may represent a unique cell type that is able to respond to EPO withdrawal by increasing permeability and interacting with phagocytic macrophages, which leads to neocytolysis.
Trial
J
J
Department of Medicine, Baylor College of Medicine, and Veterans Affairs Medical Center, Houston, Tex 77030-4211, USA. jtrial@bcm.tmc.edu
Rice
L
L
Alfrey
C P
CP
D000222:Adaptation, Physiological; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D000068817:Epoetin Alfa; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D004921:Erythropoietin / Q000008:administration & dosage*; D006461:Hemolysis; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008854:Microscopy, Electron; D008954:Models, Biological; D017467:Receptors, Erythropoietin / Q000187:drug effects / Q000502:physiology; D011994:Recombinant Proteins; D013154:Spleen / Q000098:blood supply / Q000166:cytology / Q000187:drug effects*; D014893:Weightlessness
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa