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TA Alberico, JN Ihle, CM Liang, HE McGrath and PJ Quesenberry
Hematopoietic regulatory factors produced by adherent (stromal) cells in
long-term murine bone marrow cultures have been investigated. Using an in
situ double layer agar overlay system, we demonstrated that exposure of the
stromal cells to 1,100-rad irradiation increased their activities in
stimulating colony formation of FDC-P1, an interleukin 3 (IL 3)-responsive
cell line. The colony-stimulating activities (CSAs) of the irradiated
stroma also stimulated normal marrow cells to form granulocyte-macrophage,
megakaryocyte, and mixed lineage colonies. Addition of the lectin pokeweed
mitogen to the irradiated stroma increased the level of CSAs. The FDC-P1
CSA of the irradiated stroma was inhibited by antibodies directed against
murine granulocyte- macrophage colony stimulating factor (GM-CSF) but not
by those against murine IL 3. Stromal-derived CSA for marrow cells was also
partially blocked by anti-GM-CSF antibodies, probably reflecting the
presence of other CSAs such as CSF-1. This latter growth factor has been
found to be present in conditioned media from Dexter stroma, but levels are
not increased after irradiation or lectin exposure. Partially purified GM-
CSF, like IL 3, stimulated FDC-P1 proliferation and granulocyte,
macrophage, and megakaryocyte colony formation. These results indicate that
the major terminal differentiating hormone elicited by irradiation or
lectin exposure of murine marrow stromal cells is GM-CSF. This growth
factor, along with CSF-1, can account for the differentiated progeny
produced in this system: macrophages, granulocytes, and megakaryocytes.
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| Copyright © 1987 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||