The effect of reduced oxygen tension on colony formation of erythropoietic cells in vitro.
The effect of reduced oxygen tension and the role of cellular components known to protect the cell against oxygen toxicity has been studied with respect to erythropoietic colony formation in vitro. Alphathioglycerol can be partially replaced by vitamin E and completely replaced by reduced glutathione (GSH) at physiological concentrations. Incubation of bone marrow and fetal liver early (BFU-E) and late (CFU-E) erythropoietic progenitor cells, in the presence of GSH, in an atmosphere containing 5% oxygen, 5% carbon dioxide and 90% nitrogen, as opposed to air supplemented with 5% carbon dioxide, resulted in an increase in colony numbers and response to erythropoietin (Epo). The number of colonies derived from bone marrow and fetal liver CFU-E increased by 1.2--2.8-fold with a relative Epo sensitivity increase of 3.5--4-fold. Bursts obtained from bone marrow and fetal liver BFU-E increased from 2.6- to 3.8-fold with an increased response to Epo of 2--3-fold. The effects of GSH and low oxygen tension are interpreted as causing a reduction in oxygen toxicity of the cells, thereby increasing the life span in vitro and so increasing the number of cells capable of forming colonies. The heightened response of BFU-E to Epo, analogous to the effect seen for CFU-E, implies that BFU-E may be responsive to physiological Epo concentrations at physiological oxygen tensions.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004920:Erythropoiesis; D004921:Erythropoietin / Q000097:blood; D005260:Female; D005978:Glutathione / Q000494:pharmacology; D005990:Glycerol / Q000031:analogs & derivatives / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D010101:Oxygen Consumption; D014810:Vitamin E / Q000494:pharmacology
D004921:Erythropoietin; D014810:Vitamin E; C009465:thioglycerol; D005978:Glutathione; D005990:Glycerol