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 cell s (neocytolysis) in astronauts adapting to microgravity, in polycythemic hi gh 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 physiol ogical 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 (HS EC) and investigated the responses of these cells to EPO withdrawal. Results: A monolayer of HSEC, unlike human endothelial cells from aorta, gl omerulus, or umbilical vein, demonstrated an increase in permeability upon EPO withdrawal that was accompanied by unique morphological changes. When H SEC were cultured with monocyte-derived macrophages (but not when either ce ll 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,vith phagocyti c macrophages, which leads to neocytolysis.