Stromal growth factor production in irradiated lectin exposed long-term murine bone marrow cultures.
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.
D000818:Animals; D001688:Biological Products / Q000502:physiology*; D001853:Bone Marrow / Q000502:physiology* / Q000528:radiation effects; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000502:physiology; D016207:Cytokines; D006133:Growth Substances / Q000502:physiology*; D006410:Hematopoiesis; D007158:Immunologic Techniques; D007377:Interleukin-3 / Q000502:physiology; D037102:Lectins / Q000494:pharmacology; D051379:Mice; D011043:Pokeweed Mitogens / Q000494:pharmacology
D001688:Biological Products; D003115:Colony-Stimulating Factors; D016207:Cytokines; D006133:Growth Substances; D007377:Interleukin-3; D037102:Lectins; D011043:Pokeweed Mitogens