CYTOKINE REGULATION OF THE HUMAN BURST-FORMING UNIT-MEGAKARYOCYTE

  • 1 August 1990
    • journal article
    • research article
    • Vol. 76  (3) , 516-522
Abstract
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 thrombocytopoiesis 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 auxillary cells to secondarily release additional cytokines. Information presented here indicates that the regulatory influences, acting on the different stages of megakaryocyte development, are stage-specific and accomplished by multiple cytokines.

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