Different responses of human marrow and circulating erythroid progenitors to stem cell factor, interleukin-3 and granulocyte/macrophage colony-stimulating factor.
The effects of recombinant human stem cell factor (SCF/c-kit ligand), interleukin-3 (IL-3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) on erythroid colony formation by non-phagocytic mononuclear cells (MNC) and CD34+ cells derived from normal human bone marrow (BM), peripheral blood (PB) and umbilical cord blood (CB) were studied using a methylcellulose culture containing recombinant human erythropoietin (Epo). BM-MNC generated the largest number of total erythroid colonies consisting of erythroid bursts and erythroid mixed colonies (E-Mix) in the presence of SCF, whereas PB-MNC produced the largest number with IL-3. No additive effect between SCF and IL-3 was observed in the erythroid colony formation by BM- or PB-MNC. These observations were reproducible in cultures with several independent samples and purified CD34+ cells, suggesting that in normal human adults the erythroid progenitors supported by SCF alone mainly reside in the BM but those supported by IL-3 alone are mainly circulating. IL-3 was the most potent promoter of the total erythroid colony formation by CB-MNC, but it had no cooperation with SCF. In contrast, SCF supported large numbers of E-Mix and showed significant cooperative activity with IL-3 in E-Mix formation. These findings were also confirmed using independent specimens and CD34+ cells. Outstanding E-Mix formation by the CB cells indicated that newborn infants contain significantly more immature circulating erythroid progenitors than adults. These observations will stimulate interest in the role of the c-kit-SCF system as an adhesion molecule in the ontogenetic development of hemopoiesis.
Kubo
T
T
Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan.
Nakahata
T
T
D000328:Adult; D001853:Bone Marrow / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000494:pharmacology*; D002478:Cells, Cultured; D015672:Erythroid Precursor Cells / Q000187:drug effects*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D019089:Stem Cell Factor
D015815:Cell Adhesion Molecules; D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D019089:Stem Cell Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor