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Effects of 12-0-tetradecanoylphorbol-13-acetate (TPA) on the proliferation
of granulocyte-macrophage colony-forming cells
AW Burgess and NA Nicola
It has been suggested that 12-0-tetradecanoylphorbol-13-acetate (TPA) may
stimulate the proliferation of granulocyte-macrophage (GM) colony- forming
cells (CFC) via the GM colony-stimulating factor (CSF) receptor. GM-CFC in
unfractionated mouse bone marrow and light density fetal liver (LDFL) cells
were induced by TPA to form colonies in the absence of exogenously added
GM-CSF. The colonies induced by TPA (10(- 8)M) were smaller than normally
seen with maximal concentrations of GM- CSF, and less than 30% of the
GM-CFC formed colonies in the presence of TPA. The number of colonies
stimulated by TPA in the absence of GM-CSF was dependent on the number of
cells plated. When fewer than 10,000 bone marrow cells or 3000 LDFL cells
were plated in the 1-ml semisolid agar cultures, no colonies were
stimulated by the TPA. Similarly, GM- CFC purified from the LDFL cells
stimulated with TPA did not form colonies. However, when the fetal liver
accessory cells (macrophages) were recombined with cell-sorter-purified
GM-CFC, colony formation was again observed in the presence of TPA
(10(-7)-10(-8) M). The number of colonies formed from the CFC was dependent
on the number of accessory cells present, suggesting that the macrophages
were induced by TPA to produce CSF. Although the purified GM-CFC required
CSF for proliferation, TPA (10(-8) M) increased (5-10-fold) the sensitivity
of the GM-CFC to GM-CSF. These observations indicate that TPA does not
stimulate GM-CFC proliferation directly, but rather by inducing GM-CSF
production by accessory cells and by increasing the responsiveness of
GM-CFC to GM-CSF.
Volume 61,
Issue 3,
pp. 575-579,
03/01/1983
Copyright © 1983 by The American Society of Hematology

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