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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0001675,
umls-concept:C0005953,
umls-concept:C0021757,
umls-concept:C0038250,
umls-concept:C0086418,
umls-concept:C0162371,
umls-concept:C0162768,
umls-concept:C0205171,
umls-concept:C0205195,
umls-concept:C0205409,
umls-concept:C1514485,
umls-concept:C1516960,
umls-concept:C1533691,
umls-concept:C1707455,
umls-concept:C1999177
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pubmed:issue |
10
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pubmed:dateCreated |
1995-10-4
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pubmed:abstractText |
Human interleukin-3/erythropoietin (IL-3/Epo) fusion protein have been constructed, expressed, and tested for biological activity. These fusion proteins were previously shown to be active on erythroid progenitors (BFU-E) from unseparated human bone marrow. We evaluated if these fusion proteins could stimulate erythroid and multipotential progenitor cells directly at the single-cell level. Two IL-3/Epo fusion proteins containing short (SL-3E, two amino acids) and long (LL-3E, 23 amino acids) linker sequences as well as a short linker Epo/IL-3 sequence (SL-E3, three amino acids) were tested. Highly enriched CD34 or BFU-E enriched CD34 CD33- cells from human umbilical cord blood or CD34 HLA-DR+CD33- cells from normal adult bone marrow were sorted as single cells into single wells. The combination of Epo plus IL-3 synergized to enhance the proliferation of BFU-E and multipotential progenitors (CFU-GEMM) in comparison to the individual effects of these cytokines. The three fusion proteins also enhanced proliferation of BFU-E and CFU-GEMM at the single-cell level and were at least as active as the combination of Epo and IL-3, demonstrating that IL-3/Epo fusion proteins directly stimulate proliferation of BFU-E and CFU-GEMM and that biological activity of IL-3 and Epo in vitro can be maintained when these proteins are fused. The activity of the combination of Epo and IL-3 or the fusion proteins was partially neutralized by preincubation with monoclonal antibodies to either Epo or IL-3 and was neutralized by greater than 90% by the combination of both antibodies, suggesting that the Epo and IL-3 components of the fusion proteins were both involved in the enhancing activity of these proteins. Additionally, use of monoclonal antibody to the human Epo receptor completely blocked the stimulating/enhancing activity of Epo alone, Epo plus IL-3, or the fusion proteins for stimulation of colony formation by BFU-E and CFU-GEMM but not for granulocyte-macrophage progenitors (CFU-GM), suggesting that the enhancing effects of the fusion proteins are most likely mediated, at least in part, by the Epo receptor.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0301-472X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1130-4
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7656932-Bone Marrow Cells,
pubmed-meshheading:7656932-Cell Division,
pubmed-meshheading:7656932-Cells, Cultured,
pubmed-meshheading:7656932-Erythroid Precursor Cells,
pubmed-meshheading:7656932-Erythropoiesis,
pubmed-meshheading:7656932-Erythropoietin,
pubmed-meshheading:7656932-Fetal Blood,
pubmed-meshheading:7656932-Hematopoiesis,
pubmed-meshheading:7656932-Humans,
pubmed-meshheading:7656932-Interleukin-3,
pubmed-meshheading:7656932-Recombinant Fusion Proteins,
pubmed-meshheading:7656932-Structure-Activity Relationship
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pubmed:year |
1995
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pubmed:articleTitle |
Influence in vitro of IL-3/Epo fusion proteins compared with the combination of IL-3 plus Epo in enhancing the proliferation of single isolated erythroid and multipotential progenitor cells from human umbilical cord blood and adult bone marrow.
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pubmed:affiliation |
Department of Medicine (Hematology/Oncology), Indiana University School of Medicine, Indianapolis 46202-5121, USA.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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