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Recombinant tumor necrosis factor enhances the proliferative responsiveness of murine peripheral macrophages to macrophage colony- stimulating factor but inhibits their proliferati...
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Zeitschriftentitel: | Blood |
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Personen und Körperschaften: | , |
In: | Blood, 75, 1990, 8, S. 1627-1632 |
Format: | E-Article |
Sprache: | Englisch |
veröffentlicht: |
American Society of Hematology
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Schlagwörter: |
Zusammenfassung: | <jats:p>Tumor necrosis factor (TNF) is a protein produced by activated macrophages in response to endotoxin. The effect of recombinant murine TNF (rMuTNF) on the growth of murine tissue-derived macrophage colony- forming units (CFU-M) which are responsive to both macrophage and granulocyte-macrophage colony-stimulating factors (M-CSF and GM-CSF), was studied. TNF alone did not stimulate macrophage proliferation but did prolong their survival in vitro. The proliferative response of CFU- M to M-CSF, however, was greatly enhanced by the presence of TNF. The enhancement effect of TNF is dose-dependent, reaching a maximum at approximately 50 U/mL. In contrast, the proliferative responsiveness of CFU-M to GM-CSF was inhibited by the concurrent addition of rMuTNF. Both effects appear to be caused directly by rMuTNF, rather than by the secondary factor(s) produced by TNF-treated macrophages. TNF treatment also induced a transient downmodulation of M-CSF receptors in cultured macrophages and accelerated their uptake and use of exogenous M-CSF, which may account for, at least in part, the enhanced proliferative activity in response to M-CSF. Short-term treatment (24 hours) was not sufficient to induce either an enhancing or an inhibitory effect upon CFU-M. This study suggests an autoregulatory role for TNF in the production of mature tissue macrophages by selectively enhancing their proliferative response to lineage specific growth factor, M-CSF.</jats:p> |
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Umfang: | 1627-1632 |
ISSN: |
0006-4971
1528-0020 |
DOI: | 10.1182/blood.v75.8.1627.bloodjournal7581627 |