Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-8-25
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0741-5400
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:geneSymbol
v-myc
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-72
pubmed:dateRevised
2004-11-17
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
pubmed:year
1993
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).
pubmed:affiliation
Department of Immunology, University of Alberta, Edmonton, Canada.
pubmed:publicationType
Journal Article