Linked Life Data

14604969

Source:http://linkedlifedata.com/resource/pubmed/id/14604969

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2004-3-4
pubmed:abstractText
The mechanisms regulating the homing/mobilization of hematopoietic stem/progenitor cells (HSPCs) are not fully understood. In our previous studies we showed that the complement C3 activation peptide, C3a, sensitizes responses of HSPCs to stromal-derived factor 1 (SDF-1). In this study, mobilization was induced with granulocyte colony-stimulating factor (G-CSF) in both C3-deficient (C3-/-) and C3a receptor-deficient (C3aR-/-) mice as well as in wild-type (wt) mice in the presence or absence of a C3aR antagonist, SB 290157. The data indicated (1) significantly increased G-CSF-induced mobilization in C3-/- and C3aR-/- mice compared with wt mice, (2) significantly accelerated and enhanced G-CSF-induced mobilization in wt, but not in C3-/- or C3aR-/-, mice treated with SB 290157, and (3) deposition of C3b/iC3b fragments onto the viable bone marrow (BM) cells of G-CSF-treated animals. Furthermore, mobilization studies performed in chimeric mice revealed that wt mice reconstituted with C3aR-/- BM cells, but not C3aR-/- mice reconstituted with wt BM cells, are more sensitive to G-CSF-induced mobilization, suggesting that C3aR deficiency on graft-derived cells is responsible for this increased mobilization. Hence we suggest that C3 is activated in mobilized BM into C3a and C3b, and that the C3a-C3aR axis plays an important and novel role in retention of HSPCs (by counteracting mobilization) by increasing their responsiveness to SDF-1, the concentration of which is reduced in BM during mobilization. The C3a-C3aR axis may prevent an uncontrolled release of HSPCs into peripheral blood. These data further suggest that the C3aR antagonist SB 290157 could be developed as a drug to mobilize HSPCs for transplantation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
103
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2071-8
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14604969-Animals, pubmed-meshheading:14604969-Arginine, pubmed-meshheading:14604969-Benzhydryl Compounds, pubmed-meshheading:14604969-Bone Marrow Cells, pubmed-meshheading:14604969-Bone Marrow Transplantation, pubmed-meshheading:14604969-Cell Movement, pubmed-meshheading:14604969-Complement Activation, pubmed-meshheading:14604969-Complement C3, pubmed-meshheading:14604969-Female, pubmed-meshheading:14604969-Granulocyte Colony-Stimulating Factor, pubmed-meshheading:14604969-Hematopoietic Stem Cells, pubmed-meshheading:14604969-Membrane Proteins, pubmed-meshheading:14604969-Mice, pubmed-meshheading:14604969-Mice, Inbred BALB C, pubmed-meshheading:14604969-Mice, Inbred C57BL, pubmed-meshheading:14604969-Mice, Mutant Strains, pubmed-meshheading:14604969-Radiation Chimera, pubmed-meshheading:14604969-Receptors, Complement
pubmed:year
2004
pubmed:articleTitle
Mobilization studies in mice deficient in either C3 or C3a receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow.
pubmed:affiliation
Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, 529 South Jackson St, KY 40202, USA. mzrata01@louisville.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't