Interacting cytokines regulate in vitro human megakaryocytopoiesis.
The effects of hematopoietic growth factors on in vitro human megakaryocytopoiesis were studied using a serum-depleted culture system. Both recombinant interleukin-3 (r-IL-3) and recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) increased megakaryocyte (MK) colony formation (P less than .01) above that observed in baseline cultures. Recombinant interleukin-4 (rIL-4) and interleukin 1 alpha (rIL-1 alpha) failed either to promote MK colony formation alone or to increase rIL-3 or rGM-CSF promoted colony formation. Recombinant erythropoietin (rEpo) and purified thrombocytopoiesis-stimulating factor (TSF) did not increase (P greater than .05) MK colony formation when added alone but synergized with rIL-1 alpha, leading to a twofold increase in MK colony formation. Such a synergistic relationship was not observed between rIL-4 and rEpo. In addition, TSF enhanced the ability of rIL-3 but not rGM-CSF to promote MK colony formation. Addition of rEpo to optimal or suboptimal concentrations of rGM-CSF or suboptimal concentrations of rIL-3 resulted in a significant increase (P less than .05) in the total number of MK-containing colonies, due to the appearance of multilineage colonies containing MKs. The addition of rEpo to optimal concentrations of rIL-3 resulted in increased numbers of multilineage colonies containing MKs; however, the number of total MK-containing colonies was not significantly increased when compared to assays containing rIL-3 alone. By contrast, transforming growth factor-beta (TGF-beta) inhibited both rIL-3, and rGM-CSF promoted MK colony formation, with optimal inhibition resulting in a 35%-45% reduction of MK colony formation.(ABSTRACT TRUNCATED AT 250 WORDS)
Bruno
E
E
Department of Medicine, Indiana University School of Medicine, Indianapolis 46223.
Miller
M E
ME
Hoffman
R
R
D001685:Biological Factors / Q000494:pharmacology*; D001854:Bone Marrow Cells; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D003470:Culture Media; D016207:Cytokines; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology*; D011994:Recombinant Proteins; D015291:Transforming Growth Factors / Q000494:pharmacology
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D003470:Culture Media; D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D007377:Interleukin-3; D007378:Interleukins; D011994:Recombinant Proteins; D004921:Erythropoietin; D015847:Interleukin-4; D015291:Transforming Growth Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor