Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-7-20
pubmed:abstractText
The chemokine stromal cell-derived factor-1 (SDF-1/CXCL12) and its receptor, CXCR4, are involved in a number of facets of the regulation of hematopoiesis at the level of hematopoietic stem (HSCs) and progenitor (HPCs) cells. Modulation of this ligand-receptor interaction may be of clinical utility. We now report that: (1) the CC chemokine, macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3) synergizes with AMD3100 (an antagonist of the binding of SDF-1/CXCL12 to CXCR4) to rapidly mobilize HPCs to the blood of mice; moreover, the combination of granulocyte colony-stimulating factor (G-CSF) with AMD3100 and MIP-1alpha/CCL3, given in a specific sequence, mobilizes the greatest number of HPCs compared to any combination of two of these mobilizing agents; (2) pretreatment of recipient mice with Diprotin A, an inhibitor of CD26/Dipeptidylpeptidase IV (DPPIV), enhances the competitive HSCs repopulating capacity of untreated donor cells; (3) the survival-enhancing effects of SDF-1/CXCL12 on HPCs subjected in vitro to delayed addition of growth factors (GFs) are mediated in part through the cell cycle-related proteins p21(cip1/waf1) (as assessed using p21(cip1/waf1) -/- and +/+ mice) and Mad2 (using Mad2 +/- and +/+ mice); and (4) deletion of CD26/DPPIV on mouse bone marrow cells increases the survival-enhancing effects of SDF-1/CXCL12 on HPCs. These results demonstrate the means to increase the mobilization of HPCs, the engrafting capability of HSCs, and responsiveness of HPCs to the survival-enhancing activity of SDF-1/CXCL12, effects that may be of practical value.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
1106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-19
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
AMD3100 and CD26 modulate mobilization, engraftment, and survival of hematopoietic stem and progenitor cells mediated by the SDF-1/CXCL12-CXCR4 axis.
pubmed:affiliation
Department of Microbiology and Immunology, and the Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. hbroxmey@iupui.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural