Influence of interleukins 3,5, and 6 on the growth of eosinophil progenitors in highly enriched human bone marrow in the absence of serum.
Purified preparations of natural murine interleukin (IL)-5 and recombinant human IL-1 alpha, IL-3, and IL-6 were evaluated alone, and in combination, for effects in vitro on colony formation by eosinophil progenitors (eosinophil colony-forming units, CFU-Eos) in either nonadherent low-density T-lymphocyte depleted (NALT-) or fluorescence-activated cell sorted NALT-HLA-DR+ CD34 (My10) cells from normal human bone marrow, in the absence and presence of serum. Interleukins were assessed on CFU-Eos plated directly in agar, or on CFU-Eos placed in suspension culture for 7 days prior to plating in agar in the presence of IL-5. Eosinophil colonies were identified in situ by staining with Luxol fast blue. IL-3 and IL-5 acted in agar culture as direct stimulators of CFU-Eos, using highly purified cells in the HLA-DR+ My10 fraction of cells, the specificity for CFU-Eos being greatest for IL-5 and most demonstrable in the absence of serum. The IL-3 and IL-5 direct stimulating effects on CFU-Eos were additive. IL-1 alpha and IL-6 had little or no effect, alone or in combination with IL-3 and IL-5; however, IL-3, IL-5, and IL-6 each enhanced the number of IL-5-responsive CFU-Eos found after suspension culture compared to control medium, with the individual effects being additive when the molecules were combined. These results demonstrate that both IL-3 and IL-5, alone and in combination have direct-acting effects on CFU-Eos, with the greatest specificity for stimulation of pure Eos colonies and clusters residing in IL-5, and that IL-3, IL-5, and IL-6, alone and in combination, may play a role in the survival of CFU-Eos.
Department of Medicine,(Hematology/Oncology), Indiana University School of Medicine, Indianapolis.
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Warren
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Leemhuis
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Broxmeyer
D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D000943:Antigens, Differentiation / Q000032:analysis; D001769:Blood; D001854:Bone Marrow Cells; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004804:Eosinophils / Q000166:cytology* / Q000276:immunology; D006684:HLA-DR Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D006684:HLA-DR Antigens; D007377:Interleukin-3; D015848:Interleukin-5; D015850:Interleukin-6; D011994:Recombinant Proteins