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Transforming growth factor beta inhibits megakaryocyte growth and
endomitosis
DJ Kuter, DM Gminski and RD Rosenberg
Department of Medicine, Massachusetts General Hospital, Boston.
Using a rat bone marrow culture system, the effect of transforming growth
factor beta 1 (TGF beta 1) on megakaryocyte growth and endoreduplication
has been studied. Purified human platelet TGF beta 1 inhibited the number
of megakaryocytes that appeared in culture at a half-maximal concentration
of 0.66 +/- 0.21 ng/mL and inhibited megakaryocyte endoreduplication at a
half-maximal concentration of 0.14 +/- 0.08 ng/mL. Under identical
conditions, growth of erythroid precursors was half-maximally inhibited at
a concentration of 0.125 ng/mL while myeloid growth was not inhibited at
concentrations of TGF beta 1 up to 25 ng/mL. These profound inhibitory
effects on megakaryocyte growth and endomitosis suggested that TGF beta
might play a role in megakaryocytopoiesis. Therefore, we explored the
effect of TGF beta in three different experimental situations by using a
neutralizing antibody to TGF beta: (1) Serum but not plasma was found to
inhibit the number and ploidy of megakaryocytes that grew in vitro. This
inhibitory activity was completely neutralized by antibody to TGF beta or
on treatment with dithiothreitol. (2) Plasma from thrombocytotic rats was
observed to decrease megakaryocyte ploidy on culture but this effect was
not prevented by the addition of antibody to TGF beta. (3) Plasma from
thrombocytopenic but not normal rats increased megakaryocyte ploidy on
culture. Addition of antibody to TGF beta did not alter these results.
Therefore, TGF beta is a potent inhibitor of the number and ploidy of
megakaryocytes and accounts for all the inhibition seen when megakaryocytes
are cultured in serum. However, the differences in effect on megakaryocyte
growth that we observe between normal, thrombocytopenic, and thrombocytotic
plasmas are not due to variations in the amount of TGF beta. Furthermore,
our results show that release of TGF beta from megakaryocytes during
culture does not act as an autocrine regulator of megakaryocyte ploidy in
vitro.
Volume 79,
Issue 3,
pp. 619-626,
02/01/1992
Copyright © 1992 by The American Society of Hematology
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