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Phorbol ester‐stimulated murine myelopoiesis: Role of colony‐stimulating factors
Author(s) -
Stuart Robert K.,
Sensenbrenner Lyle L.,
Shadduck Richard K.,
Waheed Abdul,
Caramatti Cecilia
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.1041170106
Subject(s) - myelopoiesis , colony stimulating factor , in vitro , cell culture , radioimmunoassay , galactocerebroside , microbiology and biotechnology , phorbol , haematopoiesis , granulocyte , granulocyte macrophage colony stimulating factor , antiserum , bioassay , biology , chemistry , biochemistry , immunology , endocrinology , protein kinase c , antibody , stem cell , central nervous system , enzyme , myelin , genetics , oligodendrocyte
Tumor promoting phorbol esters, such as 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA), stimulate colony formation in vitro by murine granulocyte‐macrophage progenitors (GM‐CFC) without added colony stimulating factors (CSF). To determine whether TPA induces CSF production in vitro, marrow cells were cultured for 1 to 7 days in liquid medium with or without TPA. No CSF was detected in any sample by a double antibody radioimmunoassay (sensitivity = 2 units/0.1 ml), however, colony‐stimulating activity was detected in supernatant fluid from all TPA containing cultures by bioassay. This activity appeared to result from a direct effect of TPA rather than from production of CSF, as equivalent activity was found in TPA‐containing medium incubated in the absence of marrow cells. Rabbit antiserum to purified L‐cell CSF inhibited colony formation stimulated by L‐cell CSF and WEHI‐3 CSF, but had no effect on colony formation induced by TPA. Cells from long‐term marrow cultures responded to TPA with colony formation, despite culture conditions and cell fractionation procedures that reduced the frequency of CSF‐proclucing macrophages to > 1.0%. TPA inhibited binding of radioiodinated L‐cell CSF to marrow cells, especially if the cells were first exposeed to TPA. These results do not support induction of CSF production as the major mechanism of phorbol ester stimulation of myelopoiesis. Phorbol esters may directly stimulate GM‐CFC and/or enhance their response to CSF by a mechanism involving CSF binding sites.