Cytokine regulation of the human burst-forming unit-megakaryocyte
RA Briddell and R Hoffman
Department of Medicine, Indiana University School of Medicine,
Indianapolis.
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.
Volume 76,
Issue 3,
pp. 516-522,
08/01/1990
Copyright © 1990 by The American Society of Hematology
