The nature of 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated hemopoiesis, colony stimulating factor (CSF) requirement for colony formation, and the effect of TPA on [125I]CSF-1 binding to macrophages.
The tumor-promoting phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) was found to act both independently of and synergistically with the mononuclear phagocyte specific colony stimulating factor (CSF-1) to stimulate the formation of macrophage colonies in cultures of mouse bone marrow cells. In contrast, TPA did not synergize with other CSF subclasses that stimulate the formation of eosinophil, eosinophil-neutrophil, neutrophil, neutrophil-macrophage, and macrophage colonies, nor with either of the two factors required for megakaryocyte colony formation, megakaryocyte CSF, and megakaryocyte colony potentiator. In serum-free mouse bone marrow cell cultures TPA retained the ability to independently stimulate macrophage colony formation. However, TPA-stimulated colony formation was suboptimal and delayed in serum-free cultures that could support optimal colony formation in the presence of CSF-1. In addition, TPA did not directly compete with [125I]CSF-1 at 4 degrees C for its specific, high-affinity receptor on mouse peritoneal exudate macrophages. However, a 2-hour preincubation of the cells with TPA at 37 degrees caused almost complete loss of the receptor. Thus, TPA is able to mimic CSF-1 in its effects on CSF-1 responsive cells in some aspects (the spectrum of target cells, the morphology of resulting colonies, and the ability to down-regulate the CSF-1 receptor) but it is not able to mimic CSF-1 in other ways (TPA alone cannot stimulate the full CSF-1 response, TPA does not stimulate the most primitive CSF-1 responsive cells, and TPA does not bind to the CSF-1 receptor).
D000818:Animals; D002460:Cell Line; D003114:Colony-Forming Units Assay; D003115:Colony-Stimulating Factors / Q000378:metabolism / Q000494:pharmacology*; D004357:Drug Synergism; D006410:Hematopoiesis / Q000187:drug effects*; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D010704:Phorbols / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D016184:Receptors, Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism / Q000494:pharmacology*
D003115:Colony-Stimulating Factors; D010704:Phorbols; D011956:Receptors, Cell Surface; D016184:Receptors, Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate