Linked Life Data

10477595

Source:http://linkedlifedata.com/resource/pubmed/id/10477595

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-10-4
pubmed:abstractText
The cytokine FLT3 ligand (FL) enhances dendritic cell (DC) generation and has therefore been proposed as a means to boost antitumor immunity. Vascular endothelial growth factor (VEGF) is produced by a large percentage of tumors and is required for development of tumor neovasculature. We previously showed that VEGF decreases DC production and function in vivo. In this study, we tested the hypothesis that VEGF regulates FL effects on DC generation. In seven experiments, four groups of mice were treated with PBS, VEGF alone (100 ng/h), FL alone (10 microgram/day), or with the combination of FL and VEGF. VEGF and PBS were administered continuously for 14 days via s.c. pumps. FL was given s.c. daily for 9 days, beginning on day 4. Tissues were collected and the number, phenotype, and function of lymph node, splenic, and thymic DCs were analyzed on day 14. As expected, treatment with FL resulted in a marked increase in the number of lymph node and spleen DCs and a smaller increase in thymic DC. Pretreatment of mice with VEGF inhibited these FL effects in lymph nodes and thymus by about 50%, whereas spleen DC numbers were undiminished by VEGF. VEGF treatment in vivo also inhibited the ability of FL to increase the number of hemopoietic precursor cells and the level of maturity exhibited by DC derived from these hemopoietic precursor cells in vitro. VEGF inhibited FL-inducible activation of transcription factor NF-kappaB. These data suggest that VEGF interferes with the ability of FL to promote dendritic cell differentiation from bone marrow progenitor cells in mice and therefore may decrease the therapeutic efficacy of FL in settings where increased numbers of DCs might provide clinical benefits.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
163
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3260-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10477595-Animals, pubmed-meshheading:10477595-Antigen Presentation, pubmed-meshheading:10477595-Antigen-Presenting Cells, pubmed-meshheading:10477595-Bone Marrow Cells, pubmed-meshheading:10477595-Cell Division, pubmed-meshheading:10477595-Cells, Cultured, pubmed-meshheading:10477595-Dendritic Cells, pubmed-meshheading:10477595-Endothelial Growth Factors, pubmed-meshheading:10477595-Female, pubmed-meshheading:10477595-Hematopoietic Stem Cells, pubmed-meshheading:10477595-Infusion Pumps, pubmed-meshheading:10477595-Injections, Subcutaneous, pubmed-meshheading:10477595-Ligands, pubmed-meshheading:10477595-Lymph Nodes, pubmed-meshheading:10477595-Lymphokines, pubmed-meshheading:10477595-Membrane Proteins, pubmed-meshheading:10477595-Mice, pubmed-meshheading:10477595-Mice, Inbred BALB C, pubmed-meshheading:10477595-Mice, Inbred C57BL, pubmed-meshheading:10477595-Mice, Inbred CBA, pubmed-meshheading:10477595-Spleen, pubmed-meshheading:10477595-Vascular Endothelial Growth Factor A, pubmed-meshheading:10477595-Vascular Endothelial Growth Factors
pubmed:year
1999
pubmed:articleTitle
Effect of vascular endothelial growth factor and FLT3 ligand on dendritic cell generation in vivo.
pubmed:affiliation
Department of Medicine, Vanderbilt Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.