title: Further examination of the effects of recombinant cytokines on the proliferation of human megakaryocyte progenitor cells.
abstract: The effect of several recombinant cytokines, including interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and IL-1 alpha, on megakaryocyte (MK) colony formation by a normal human bone marrow subpopulation (CD34+ DR+), enriched for the MK colony-forming unit (CFU-MK), was studied using a serum-depleted, fibrin clot culture system. IL-3 and GM-CSF, but not IL-6 or IL-1 alpha, stimulated MK colony formation by CD34+ DR+ cells. However, the addition of IL-1 alpha to CD34+ DR+ cultures containing IL-6 resulted in the appearance of CFU-MK-derived colonies, suggesting that IL-6 requires the presence of IL-1 alpha to exhibit its MK colony-stimulating activity (MK-CSA). Addition of neutralizing antibodies to IL-3 and GM-CSF, but not to IL-6 and IL-1 alpha, specifically inhibited the MK-CSA of IL-3 and GM-CSF, respectively. The addition of either anti-IL-6, anti-IL-1 alpha, or anti-IL-3 antisera to cultures containing both IL-6 and IL-1 alpha totally abolished the MK-CSA of the IL-6/IL-1 alpha combination. However, neither anti-IL-3 nor anti-GM-CSF antisera could totally neutralize the additive effect of the combination of IL-3 and GM-CSF on MK colony formation, indicating that these two cytokines act by affecting distinct effector pathways. These results suggest that while IL-3 and GM-CSF can directly affect CFU-MK-derived colony formation, IL-1 alpha and IL-6 act in concert to promote de novo elaboration of IL-3 and thereby promote CFU-MK proliferative capacity.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis.
authors.forename: E
authors.initials: E
authors.lastname: Bruno
authors.forename: R J
authors.initials: RJ
authors.lastname: Cooper
authors.forename: R A
authors.initials: RA
authors.lastname: Briddell
authors.forename: R
authors.initials: R
authors.lastname: Hoffman
mesh_terms: D000906:Antibodies; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34; D001854:Bone Marrow Cells; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D004347:Drug Interactions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008533:Megakaryocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D018952:Antigens, CD34; D016207:Cytokines; D006684:HLA-DR Antigens; D007375:Interleukin-1; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor