Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1997-10-1
pubmed:abstractText
To determine the hematopoietic actions of recombinant human c-Mpl ligand (thrombopoietin [TPO]), we studied its effects on the proliferation and differentiation of highly purified CD34+ blood progenitors in plasma-containing and serum-free culture. TPO alone promoted the growth of small megakaryocyte colonies (CFU-Meg) in numbers two to three times greater than those produced by interleukin (IL)-3. The combination of TPO and stem cell factor (SCF) exerted a significant synergistic effect on CFU-Meg formation. In the presence of TPO and IL-3 or granulocyte/macrophage-colony stimulating factor (GM-CSF), a significant number of mixed colonies (CFU-Mix) were observed. The combination of TPO and Epo did not increase the number of CFU-Meg, but did support erythroid-burst (BFU-E) and CFU-Mix colony formation. Interestingly, the combination of TPO with cytokines known to have burst-promoting activity (BPA), including IL-3, GM-CSF, IL-9, and SCF, increased the number of BFU-E and CFU-Mix in the presence of Epo. The BPA of TPO was further investigated by delayed addition of Epo on day 6 after incubation with TPO from day 0. None of the BFU-E or CFU-Mix survived, indicating that TPO acted as a costimulant exclusively for Epo. Moreover, a neutralizing anti-human Mpl receptor polyclonal antibody completely abrogated the BPA of TPO, demonstrating that this effect was mediated through the Mpl receptor. Finally, experiments in single-cell clone sorting and serum-free culture clearly demonstrated that a combination of TPO and Epo directly supported BFU-E and CFU-Mix. These results suggest that TPO acts not only in megakaryocytopoiesis but also in the early stage of hematopoiesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1025-33
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9293899-Antigens, CD34, pubmed-meshheading:9293899-Dose-Response Relationship, Drug, pubmed-meshheading:9293899-Erythroid Precursor Cells, pubmed-meshheading:9293899-Erythropoiesis, pubmed-meshheading:9293899-Erythropoietin, pubmed-meshheading:9293899-Granulocyte-Macrophage Colony-Stimulating Factor, pubmed-meshheading:9293899-Hematopoiesis, pubmed-meshheading:9293899-Hematopoietic Cell Growth Factors, pubmed-meshheading:9293899-Humans, pubmed-meshheading:9293899-Interleukin-3, pubmed-meshheading:9293899-Male, pubmed-meshheading:9293899-Megakaryocytes, pubmed-meshheading:9293899-Neoplasm Proteins, pubmed-meshheading:9293899-Proto-Oncogene Proteins, pubmed-meshheading:9293899-Receptors, Cytokine, pubmed-meshheading:9293899-Receptors, Thrombopoietin, pubmed-meshheading:9293899-Testicular Neoplasms, pubmed-meshheading:9293899-Thrombopoietin
pubmed:year
1997
pubmed:articleTitle
Recombinant human c-Mpl ligand (thrombopoietin) not only acts on megakaryocyte progenitors, but also on erythroid and multipotential progenitors in vitro.
pubmed:affiliation
Second Department of Surgery, Kyoto Prefectural University of Medicine, Kamigyoku, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't