Transforming growth factor beta inhibits endomitosis in the Dami human
megakaryocytic cell line
SM Greenberg, C Chandrasekhar, DE Golan and RI Handin
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
Megakaryocyte development is a carefully controlled process that is at
least partially regulated by cytokines. Previous investigations of
megakaryocyte development have focused primarily on defining growth factors
that induce or enhance differentiation. In this study we demonstrate that a
specific cytokine, transforming growth factor beta 1 (TGF beta 1), inhibits
the phorbol myristate acetate (PMA)-induced differentiation of the Dami
human megakaryocytic cell line. The addition of purified platelet TGF beta
1 inhibits PMA-induced endomitosis in a dose-dependent manner. Inhibition
of endomitosis occurs with as little as 0.4 pmol/L TGF beta 1, is
half-maximal at 6.4 pmol/L, and is maximal between 40 and 200 pmol/L TGF
beta 1. Inhibition does not require other growth factors or
nonmegakaryocytic cells. Removal of TGF beta 1 from the cultures decreases
inhibition, suggesting that the continuous presence of TGF beta 1 is
required and that its effects are reversible. This effect occurs even
though the Dami cells constitutively express TGF beta 1 messenger RNA
(mRNA) and the TGF beta 1 mRNA levels are increased by PMA. TGF beta 1 also
has been shown to inhibit endomitosis during short-term culture of primary
human megakaryocytes. These results suggest a model in which negative as
well as positive regulatory factors modulate a critical stage of
megakaryocyte development.
Volume 76,
Issue 3,
pp. 533-537,
08/01/1990
Copyright © 1990 by The American Society of Hematology
