Tumor necrosis factor-α inhibits generation of glycophorin A + cells by CD34 + cells

• Published in: Experimental hematology 2002-11, Vol.30 (11), p.1238-1247
• Main Authors: Xiao, Weiguo, Koizumi, Kazuki, Nishio, Mitsufumi, Endo, Tomoyuki, Osawa, Mitsujiro, Fujimoto, Katsuya, Sato, Ikumi, Sakai, Toshiya, Koike, Takao, Sawada, Ken-ichi
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD - analysis; Antigens, CD34 - analysis; Antigens, Differentiation - analysis; Cell Differentiation - drug effects; Cell Division - drug effects; Cells, Cultured - drug effects; Colony-Forming Units Assay; Erythroid Precursor Cells - cytology; Erythroid Precursor Cells - drug effects; Erythropoiesis - drug effects; Filgrastim; Glycophorin - analysis; Granulocyte Colony-Stimulating Factor - pharmacology; Hematopoietic Stem Cell Mobilization; Humans; Receptors, Tumor Necrosis Factor - analysis; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Recombinant Proteins; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0301-472X; 1873-2399
• DOI: 10.1016/S0301-472X(02)00930-X

The inhibitory effects of tumor necrosis factor-α (TNF-α) on cytokine-induced proliferation and differentiation of normal human erythroid progenitors have been characterized extensively, yet little is known about the maturation level of erythroid progenitors that are sensitive to TNF-α or of the expression of TNF receptors (TNFRs) in erythroid lineage. The aim of this study was to determine the extent to which human erythroid progenitor cells are sensitive to TNF-α, and to relate this to the expression of TNFRs in the erythroid lineage. Highly purified human CD34 + cells underwent erythroid differentiation, with or without TNF-α. We used colony assay as well as a method by which colony-forming unit-erythroid (CFU-E) and glycophorin A (GPA; a specific marker for erythroid lineage) positive cells can be generated in liquid phase from purified human CD34 + cells in the presence of multiple cytokines, including stem cell factor (SCF), interleukin-3 (IL-3), and erythropoietin (EPO). During erythroid differentiation of CD34 + cells, TNFRs expression were monitored. TNF-α inhibited the generation of GPA + cells by CD34 + cells as well as the proliferative capacity of GPA + cells supported by EPO, IL-3, and SCF. Erythroid progenitors became resistant to the inhibitory effect of TNF-α as they matured. The detectable expression of TNFR-I was transient in the early phase of erythroid differentiation, whereas TNFR-II was expressed through the entire course of erythroid differentiation of CD34 + cells. TNF-α suppresses erythropoiesis by inhibiting the generation of GPA + cells derived from CD34 + cells as well as by inhibiting the proliferative capacity of GPA + cells. Although the presence of TNFRs does not directly indicate that the receptor(s) mediates death signaling, altered expression of TNFRs depending on the level of maturation may imply altered sensitivities to TNF-α in various stage of erythroid progenitors.