In vitro differentiation and proliferation of human hematopoietic progenitors: the effects of interleukins 1 and 6 are indirectly mediated by production of granulocyte-macrophage colony-stimulating factor and interleukin 3.
The effect of recombinant human interleukin (IL)-1 and IL-6 on the differentiation and proliferation in vitro of human granulocyte-macrophage (GM) and erythroid progenitors has been investigated in either fetal bovine serum (FBS)-supplemented or FBS-deprived cultures. Sources of progenitor cells were unfractionated bone marrow cells or marrow cells depleted of adherent and/or T cells. Each interleukin was investigated either alone or in combination with GM-colony-stimulating factor (CSF), IL-3 and erythropoietin (Epo), or granulocyte (G)-CSF. In FBS-supplemented cultures of unfractionated marrow cells, IL-1 induced optimal GM colony growth and increased by 50% the number of erythroid bursts that formed in the presence of Epo. The addition to these cultures of a neutralizing anti-GM-CSF monoclonal antibody or of an anti-IL-3 serum decreased the growth of GM colonies by 80% and 40%, respectively. Under the same conditions, IL-6 had no effect on GM colony growth but increased by 90% the number of erythroid bursts. This effect was partially (40%) neutralized by addition of anti-IL-3 serum. IL-1 and IL-6 were weak stimuli, or had no effect at all, either alone or in combination with GM-CSF and IL-3 in FBS-deprived cultures or in FBS-supplemented cultures of nonadherent or nonadherent, T-cell-depleted marrow cells. IL-1 and IL-6 had no effect, either alone or in combination with IL-3, in maintaining the number of progenitor cells in short-term liquid suspension cultures. These results indicate that the actions of IL-1 and IL-6 on hematopoiesis are mainly indirect and mediated by the production of GM-CSF and/or IL-3 by accessory cells. However, neither IL-1 nor IL-6 alone is sufficient to stimulate production of growth factor(s) by accessory cells, and at least a second stimulus, provided by FBS, is also required. These data are in agreement with a multisignal model of regulation of the expression of growth factor genes.
Migliaccio
G
G
Laboratory of Hematopoietic Growth Factors, New York Blood Center, NY 10021.
Migliaccio
A R
AR
Adamson
J W
JW
D000906:Antibodies / Q000276:immunology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000276:immunology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007377:Interleukin-3 / Q000096:biosynthesis* / Q000276:immunology; D015850:Interleukin-6 / Q000494:pharmacology*
D000906:Antibodies; D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D016178:Granulocyte-Macrophage Colony-Stimulating Factor