Cytokine regulation of the human burst-forming unit-megakaryocyte.
The human burst-forming unit-megakaryocyte (BFU-MK) is a primitive megakaryocytic progenitor cell. A marrow cell population enriched for BFU-MK (CD34+ DR-) was obtained by monoclonal antibody labeling and fluorescence-activated cell sorting. CD34+DR- cells were assayed in a serum-depleted, fibrin clot culture system. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), recombinant interleukin-3 (rIL-3), and megakaryocyte colony-stimulating factor (MK-CSF), partially purified from human plasma, were each individually capable of promoting BFU-MK-derived colony formation. Recombinant erythropoietin, rG-CSF, rIL-4, rIL-6, and thrombocytopiesis stimulating factor, partially purified from human embryonic kidney cell conditioned media, had no stimulatory effect on BFU-MK-derived colony formation when added alone or in various combinations with either GM-CSF, IL-3, or MK-CSF, GM-CSF and IL-3, GM-CSF and MK-CSF, but not IL-3 and MK-CSF had additive actions in promoting BFU-MK-derived colony formation, rIL-1 alpha had no influence alone on BFU-MK cloning efficiency, but had a dose-dependent, synergistic effect with IL-3, but not with GM-CSF or MK-CSF. The synergistic relationship between IL-1 alpha and IL-3 was abrogated by addition of an IL-1 alpha neutralizing antibody but not by a GM-CSF neutralizing antiserum, suggesting that IL-1 alpha acts directly on the BFU-MK and not by stimulating marrow auxiliary cells to secondarily release additional cytokines. Information presented here indicates that the regulatory influence, acting on the different stages of megakaryocyte development, are stage-specific and accomplished by multiple cytokines.
Briddell
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RA
Department of Medicine, Indiana University School of Medicine, Indianapolis.
Hoffman
R
R
D001685:Biological Factors / Q000494:pharmacology*; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D016207:Cytokines; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000187:drug effects*; D058851:GPI-Linked Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects*; D008562:Membrane Glycoproteins; D000090204:Mesothelin; D011506:Proteins / Q000494:pharmacology
D001685:Biological Factors; D003115:Colony-Stimulating Factors; D016207:Cytokines; D058851:GPI-Linked Proteins; D006133:Growth Substances; D007377:Interleukin-3; D008562:Membrane Glycoproteins; D011506:Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000090204:Mesothelin