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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 [ 125 I]CSF‐1 binding to macrophages
Author(s) -
Guilbert L. J.,
Nelson D. J.,
Hamilton J. A.,
Williams N.
Publication year - 1983
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041150310
Subject(s) - megakaryocyte , macrophage colony stimulating factor , colony stimulating factor , haematopoiesis , eosinophil , biology , macrophage , 12 o tetradecanoylphorbol 13 acetate , bone marrow , receptor , microbiology and biotechnology , medicine , immunology , chemistry , biochemistry , stem cell , signal transduction , protein kinase c , in vitro , phorbol ester , asthma
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 [ 125 I]CSF‐1 at 4°C for its specific, high‐affinity receptor on mouse peritoneal exudate macrophages. However, a 2‐hour preincubation of the cells with TPA at 37° 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).