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Soluble thrombopoietin receptor (Mpl) and granulocyte colony- stimulating
factor receptor directly stimulate proliferation of primitive hematopoietic
progenitors of mice in synergy with steel factor or the ligand for
Flt3/Flk2
H Ku, F Hirayama, T Kato, H Miyazaki, M Aritomi, Y Ota, AD D'Andrea, SD Lyman and M Ogawa
Department of Medicine, Medical University of South Carolina, Charleston,
USA.
In an effort to establish the specificity of the thrombopoietin (TPO)
effects on murine multipotential progenitors, we tested the effects of
soluble TPO receptor (sTPOR; sMpl) on multilineage colony formation that
was supported by a combination of TPO and steel factor (SF). Surprisingly,
sTPOR did not suppress colony formation from primitive progenitors. This
led to the discovery that sTPOR synergizes with SF or Flt3/Flk2 ligand (FL)
to support the formation of various types of hematopoietic colonies
including multilineage colonies. The colonies supported by the combination
of sTPOR and SF were capable of expressing both myeloid and B-lymphoid
potentials. Studies using micromanipulation and serum-free culture showed
that the effects of sTPOR and SF on the primitive progenitors are direct,
not mediated by contaminating stromal cells, and not dependent on factors
present in the serum. TPOR belongs to the cytokine receptor group that
includes granulocyte colony- stimulating factor receptor (G-CSFR) and
erythropoietin receptor (EPOR). Therefore, we tested the effects of sG-CSFR
and sEPOR on primitive progenitors. sG-CSFR, but not sEPOR, was able to
synergize with SF or FL in supporting the proliferation of primitive
progenitors. The direct effects of the soluble receptors appear to be
mediated through interactions with their respective membrane-bound
receptors expressed on the primitive hematopoietic progenitors.
Volume 88,
Issue 11,
pp. 4124-4131,
12/01/1996
Copyright © 1996 by The American Society of Hematology
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