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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1993-8-25
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pubmed:abstractText |
Tumor necrosis factor alpha (TNF-alpha) more than doubles tritiated thymidine ([3H]TdR) uptake in mouse macrophages stimulated by macrophage colony-stimulating factor (CSF-1). However, nothing is known of how TNF-alpha affects this increase or even whether it is manifested by increased cellular proliferation. Here we characterize the effects of TNF-alpha on CSF-1-stimulated proliferation of both primary cells (bone marrow-derived macrophages, BMMs) and a cloned growth factor-dependent macrophage cell line (S1). We show that the TNF-alpha-induced increase in [3H]TdR uptake of CSF-1-stimulated macrophages is directly proportional to an increase in the DNA content of the culture and that the effects of TNF-alpha are direct and independent of cell number. TNF-alpha decreases the population doubling time of log-phase growing macrophages having quite different growth rates to the same (approximately 30%) extent: the doubling time of BMMs decreases from 24 to 17 h and that of S1 cells from 17 to 13 h. TNF-alpha exerts its effects on log-phase growth by increasing to the same proportion CSF-1-stimulated proliferation at all concentrations of CSF-1; that is, TNF-alpha does not shift, but rather amplifies, the CSF-1 dose-response curve. Although TNF-alpha alone does not stimulate macrophage proliferation, its presence in S1 cell cultures coming to quiescence after withdrawal of CSF-1 greatly increases subsequent CSF-1-stimulated [3H]TdR uptake as the cells reenter the cycle. Finally, we show that both human and mouse TNF-alpha increase CSF-1-stimulated log-phase growth and reentry of quiescent cells into the cycle equally on a molar basis (half-maximal stimulation of approximately 0.3 nM). The latter observation argues that the growth-stimulatory effects of TNF-alpha are mediated via the 55-60-kd TNF receptor. We conclude that TNF-alpha acts directly on growth-competent macrophages to decrease significantly the population doubling time in a manner that enhances the mitogenic effects of CSF-1.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Growth Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Macrophage Colony-Stimulating Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine,
http://linkedlifedata.com/resource/pubmed/chemical/Tritium,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0741-5400
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
54
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pubmed:geneSymbol |
v-myc
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
65-72
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:8336080-Animals,
pubmed-meshheading:8336080-Cell Count,
pubmed-meshheading:8336080-Cell Cycle,
pubmed-meshheading:8336080-Cell Division,
pubmed-meshheading:8336080-Cell Line, Transformed,
pubmed-meshheading:8336080-Cells, Cultured,
pubmed-meshheading:8336080-DNA,
pubmed-meshheading:8336080-Drug Synergism,
pubmed-meshheading:8336080-Female,
pubmed-meshheading:8336080-Growth Substances,
pubmed-meshheading:8336080-Humans,
pubmed-meshheading:8336080-Kinetics,
pubmed-meshheading:8336080-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:8336080-Macrophages,
pubmed-meshheading:8336080-Mice,
pubmed-meshheading:8336080-Mice, Inbred C3H,
pubmed-meshheading:8336080-Mitogens,
pubmed-meshheading:8336080-Stimulation, Chemical,
pubmed-meshheading:8336080-Thymidine,
pubmed-meshheading:8336080-Tritium,
pubmed-meshheading:8336080-Tumor Necrosis Factor-alpha
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pubmed:year |
1993
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pubmed:articleTitle |
Analysis of the synergistic stimulation of mouse macrophage proliferation by macrophage colony-stimulating factor (CSF-1) and tumor necrosis factor alpha (TNF-alpha).
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pubmed:affiliation |
Department of Immunology, University of Alberta, Edmonton, Canada.
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pubmed:publicationType |
Journal Article
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