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A single injection of pegylated murine megakaryocyte growth and development
factor (MGDF) into mice is sufficient to produce a profound stimulation of
megakaryocyte frequency, size, and ploidization
JT Arnold, NC Daw, PE Stenberg, D Jayawardene, DK Srivastava and CW Jackson
Division of Experimental Hematology, St Jude Children's Research Hospital,
Memphis, TN 38105, USA.
Despite numerous studies investigating the action of c-mpl ligand, no
reports have defined the in vivo changes in megakaryocytopoiesis in
response to a single injection of this cytokine. Here we compare the
kinetics of the megakaryocytopoietic response in C57BI/6J mice administered
25 micrograms/ kg or 250 micrograms/kg of pegylated (PEG) murine
megakaryocyte growth and development factor (MGDF) as a single intravenous
injection. Megakaryocytes of mice treated with MGDF had normal
ultrastructure, showing a typical distribution of the demarcation membrane
system, alpha-granules, and other cytoplasmic organelles. Megakaryocyte
ploidy, size, and frequency were markedly increased with both MGDF doses.
Megakaryocyte ploidy was maximally increased from a modal value of 16N to
64N on day 3, with both doses of MGDF. Similarly, a comparable increase in
megakaryocyte size occurred in the two MGDF groups. Increased megakaryocyte
size was coupled to the increase in megakaryocyte ploidy, and no evidence
for independent regulation of megakaryocyte size within individual ploidy
classes was apparent. In contrast to megakaryocyte ploidy and size, the
increase in megakaryocyte frequency was markedly different with the two
doses of MGDF. The proportion of 2N and 4N cells was increased from a
baseline of 0.035% to 0.430% by day 4 in mice treated with the higher dose
of MGDF, but only to 0.175% in mice administered 25 micrograms/kg of MGDF.
The marked increase in the pool of these immature megakaryocytes translated
to a sustained elevation in the frequency of polyploid megakaryocytes (8N
cells and greater). In contrast to the sustained increase in the frequency
of polyploid cells, the level of polyploidization was downregulated on days
6 to 10, but normalized by day 14. We conclude that a single injection of
MGDF is able to expand the megakaryocytic pool in a dose-dependent manner,
which, with subsequent maturation, should lead to an increased rate of
platelet production.
Volume 89,
Issue 3,
pp. 823-833,
02/01/1997
Copyright © 1997 by The American Society of Hematology
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