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Blood, Vol. 95 No. 2 (January 15), 2000:
pp. 503-509
Recombinant human interleukin-11 synergizes with steel factor
and interleukin-3 to promote directly the early stages of
murine megakaryocyte development in vitro
Nadine S. Weich,
Michael Fitzgerald,
Anlai Wang,
James Calvetti,
Joanne Yetz-Aldape,
Steven Neben, and
Katherine J. Turner
From the Department of Tissue Growth and Repair and the Department
of Immunology, Genetics Institute, Cambridge, MA.
The authors studied the role that interleukin (IL)-11 plays
during the early stages of megakaryocyte (MK) development by
investigating its in vitro effects on cell subpopulations enriched for
bone marrow primitive progenitor cells and early and late committed progenitor cells. Progenitor subpopulations were isolated from bone
marrow of normal or 5-fluorouracil (5FU)-treated mice and separated by
sorting based on the surface antigens Sca-1, c-kit, and CD34.
Functional analysis of the cell subpopulations, 5FU Lin Sca-1+c-kit+ or normal
bone marrow (NBM)
LinSca-1+c-kit+CD34cells,
indicated that exposure of these cells to recombinant human (rh)IL-11
in combination with steel factor (SF) stimulates the formation of
colonies in methylcellulose and their proliferation in single
cell-containing liquid cultures. Kinetic studies of MK progenitor
generation, in response to SF and rhIL-11, demonstrated that a
significant number of the progenitors produced are committed to the MK
lineage. RhIL-11 also synergized with both SF and IL-3 to stimulate MK
colony growth from NBM
LinSca-1+c-kit+ cells (early
progenitors) and NBM
LinSca-1c-kit+ cells
(committed late progenitors). In the presence of IL-3, NBM,
LinSca-1c-kit+ cells
responded more strongly to rhIL-11 than SF. Consistent with these
results is the observation that IL-11 receptor  chain mRNA is
present in all the progenitor cells from which the MKs are derived.
This cell culture and RNA analysis suggest that murine bone marrow
primitive progenitor cells and early and late progenitor cells are
direct targets of rhIL-11 and that rhIL-11 has the potential to promote
megakaryocyte development at several very early stages. (Blood,
2000;95:503-509)
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