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HEMATOPOIESIS
From the Division of Hematology/Oncology, Hunter Holmes
McGuire Department of Veterans Affairs Medical Center, and the Medical
College of Virginia, Virginia Commonwealth University, Richmond, VA.
When interleukin-2 (IL-2) was added to immature, low-ploidy
(greater than 80% 2N+4N) megakaryocytes generated in IL-3 and stem
cell factor (SCF)-containing liquid cultures of blood mononuclear cells highly enriched in hematopoietic progenitors, a 2- to 6-fold increase in the absolute number of polyploid (more than 8N)
megakaryocytes was noted. This effect was found to be indirect and was
mediated through natural killer (NK) cells that constitute the major
lymphoid cell contaminating day 6 megakaryocyte cell populations. IL-2 had no effect on megakaryocytes generated from CD34+ cells
stimulated with IL-3 and SCF. However, medium conditioned by
IL-2-stimulated, but not resting, NK cells (NKCM) contained a
trypsin-sensitive factor capable of increasing 2- to 5-fold the number
of polyploid megakaryocytes generated in vitro from IL-3 and
SCF-stimulated CD34+ cells. The activity in NKCM was dose
dependent and could not be neutralized by an excess of antibodies to
IL-6, IL-11, leukemia inhibitory factor (LIF), gp130, stromal
cell derived factor-1a (SDF-1a), and thrombopoietin (TPO). Addition of
IL-11, but not TPO, to NKCM-containing cultures resulted in further
augmentation of polyploidy, with the generation of 50% to 70%
polyploid megakaryocytes with a modal ploidy of 16N. This factor is
distinct from TPO because it induces endomitosis in IL-3-generated
megakaryocytes in vitro, whereas TPO does not, and its activity on
megakaryocyte ploidy is not altered by optimal concentrations of TPO.
In addition, no message for TPO is detectable in IL-2-stimulated NK
cells by reverse transcription-polymerase chain reaction. These
findings indicate that IL-2-stimulated NK cells produce a novel
peptide, distinct from TPO, IL-6, IL-11, LIF, other gp130-associated
interleukins, and SDF1a, that can induce in vitro endomitosis in
immature human megakaryocytes in the presence of IL-3 and SCF. This article has been cited by other articles:
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| Copyright © 2002 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||