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N Dainiak, D Sutter and S Kreczko
To investigate cellular mechanisms involved in thyroid hormone stimulation
of erythropoiesis, we studied the response of erythroid burst-forming unit
(BFU-E) proliferation to L-triiodothyronine (L-T3) in a serum-free culture
system. When added directly to culture, L-T3 stimulates erythroid burst
formation by normal human bone marrow cells. In contrast,
granulocyte-macrophage colony formation is unaffected. Enhancement of
erythroid burst formation by L-T3 required the presence of nylon wool
adherent and/or B-4 antigen-positive light-density marrow populations.
Addition of other erythropoietic factors including platelet-derived growth
factor and insulinlike growth factor II did not abrogate this apparent
cellular requirement. Pulse exposure of marrow and peripheral blood
mononuclear cells (greater than 95% lymphocytes) to L-T3 accelerates the
release of a soluble factor that augments BFU-E proliferation into
serum-free liquid culture medium. Time-course studies show that this factor
appears in conditioned medium (CM) coincidentally with erythroid
burst-promoting activity (BPA). Furthermore, incubation of CM with an
antibody known to react with and adsorb BPA from solution removes the
inducible mitogen. Biochemical analysis of CM prepared from unexposed and
L-T3 pulse-exposed cells indicates that the rate of protein appearance is
accelerated by L-T3 in a fashion that immediately precedes growth factor
release and that several polypeptides are quantitatively increased. We
conclude that unlike erythropoietin, which is mitogenic for progenitor
cells directly, L-T3 enhances BFU-E proliferation indirectly by augmenting
the release of soluble BPA-like molecules from accessory cells in culture.
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| Copyright © 1986 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||