Synergistic effect of recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic progenitors.
Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-gamma (IFN-gamma) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL-3, IFN-gamma directly stimulated the growth of blood progenitors in a dose-dependent manner with single-hit kinetics, whereas IFN-gamma suppressed the growth of G-CSF-supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-gamma on progenitor growth. These results suggest that the inhibitory effect of IFN-gamma on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-gamma may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells.
Kawano
Y
Y
Department of Pediatrics, University Hospital, Tokushima, Japan.
Takaue
Y
Y
Hirao
A
A
Abe
T
T
Saito
S
S
Matsunaga
K
K
Watanabe
T
T
Hirose
M
M
Ninomiya
T
T
Kuroda
Y
Y
D001781:Blood Component Removal; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology*; D008747:Methylcellulose; D011994:Recombinant Proteins / Q000494:pharmacology
D007377:Interleukin-3; D011994:Recombinant Proteins; D007371:Interferon-gamma; D008747:Methylcellulose