Acetylcholinesterase in the human erythron. III. Regulation of differentiation.
Acetylcholinesterase (AChE) is present in both primitive and mature erythroid cells, but a role for the enzyme in human hematopoiesis has not been defined. This prospect represented the primary objective of the following study. In clonal culture of normal human bone marrow cells, a "wave" of AChE activity was demonstrated, rising from undetectable levels to a peak (of 1.48 femto-moles per min per cell) at 10 days in the course of progressive erythroid clonogenesis. At concentrations of enzyme inhibitor that clearly reduced AChE activity in a dose-dependent fashion, there was no overall effect on erythropoiesis in vitro, but the clones were generally smaller and significantly more often multi-focal than in control cultures. Furthermore, in the presence of AChE inhibitors, a concentration-dependent increase in the myeloid-erythroid ratios of the culture harvests was observed. Likewise, a clear reduction in hemoglobination was revealed, in cells of 10 day cultures, from a mean hemoglobin concentration of 35.0 pg per cell in controls to 20.1 pg per cell in the presence of the maximal concentration of the inhibitor (10(-6) M eserine). These data point to a role for AChE in the regulation of differentiation in the human erythron.
Barr
R D
RD
Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Koekebakker
M
M
D000110:Acetylcholinesterase / Q000378:metabolism* / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002455:Cell Division; D002470:Cell Survival; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003114:Colony-Forming Units Assay; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000201:enzymology*; D006454:Hemoglobins / Q000096:biosynthesis; D006801:Humans
D002800:Cholinesterase Inhibitors; D006454:Hemoglobins; D000110:Acetylcholinesterase