Effects of recombinant human G-CSF, GM-CSF, IL-3, and IL-1 alpha on the
growth of purified human peripheral blood progenitors
Y Takaue, Y Kawano, CL Reading, T Watanabe, T Abe, T Ninomiya, E Shimizu, T Ogura, Y Kuroda and A Yokobayashi
Department of Pediatrics, University Hospital of Tokushima, Japan.
The effects of recombinant products of granulocyte colony-stimulating
factors (G-CSF), granulocyte/macrophage CSF (GM-CSF), human interleukin- 3
(IL-3), and interleukin-1 (IL-1) were studied using purified target cell
populations from patients undergoing peripheral blood stem cell
transplantation after myeloablative therapy. Cells were subjected to
combined purification procedures including negative selection with a panel
of monoclonal antibodies (CD2, 3, 5, 10, and 20). The purified cells were
enriched for HLA-DR+ (51% to 71%) and My-10+ (CD34; 37% to 54%) and had a
plating efficiency of up to 20%. In the liquid- suspension limiting
dilution clonal assay (LDA), purified progenitors responded directly to
IL-3 by proliferation with single-hit kinetics. The ability of GM-CSF to
support progenitor growth was inferior to that of IL-3, and the cells were
virtually unresponsive when cultured with G- CSF, supporting the notion
that these blood-derived progenitors belong to a primitive population of
hematopoietic progenitor cells. The results obtained in simultaneous
methycellulose cultures (MC) showed the same trend and provided additional
information on the ability of GM- CSF and IL-3 to support erythroid
progenitor growth. The combination of IL-3 plus G-CSF, but not IL-3 plus
GM-CSF, resulted in a synergistic increase in colony number. IL-1 alpha
increased both the size and number of colonies when added to IL-3 or G-CSF.
Study of this enriched progenitor cell population in MC and LDA represents
an excellent model for the investigation of myeloid and erythroid
differentiation and for evaluating the influence of various cytokines on
human hematopoiesis.
Volume 76,
Issue 2,
pp. 330-335,
07/15/1990
Copyright © 1990 by The American Society of Hematology