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JS Greenberger, PE Newburger and M Sakakeeny
The effects of the tumor-promoter phorbol myristate acetate (PMA) on normal
hemopoiesis and Friend leukemia virus (FLV) granulocytic leukemogenesis in
long-term bone marrow cultures were examined. FLV- anemia-inducing strain
(FLV-A) infected, Rauscher R-MuLV clone M52R infected, or uninfected
control NIH Swiss mouse marrow cultures were treated weekly with PMA or
4-O-methyl-PMA at 2.0 ng/ml or 200.0 ng/ml. Addition of PMA to control
uninfected or R-MuLV-infected cultures decreased production of nonadherent
granulocytic cells and granulocyte- macrophage progenitor cells (GM-CFU-c),
and increased the numbers of adherent macrophages. Addition of PMA to
FLV-A-infected cultures did not inhibit generation of granulocytic leukemia
cell lines even though the numbers of adherent adipocytes were decreased
and adherent macrophages were increased. PMA treatment of freshly explanted
whole bone marrow but not purified nonadherent GM-progenitor cells from
long- term bone marrow cultures stimulated GM-CFU-c and cluster formation
in the absence of added colony-stimulating factor (CSF). The sensitivity of
purified GM-progenitor cells to L929 or WEHI-3 CSF was not altered by PMA;
however, PMA treatment of bone marrow macrophages or peritoneal exudate
macrophages stimulated detectable GM-CFU-c and cluster formation by
purified GM-progenitor cells under conditions where equal numbers of
untreated macrophages failed to be stimulatory. Thus, several PMA effects
on hempoietic stem cells in vitro are mediated through indirect action on
adherent stromal cells including macrophages.
This article has been cited by other articles:
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| Copyright © 1980 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||
