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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-12-16
pubmed:abstractText
Bone marrow from wild-type mice and mice with mutated Fas (lpr) or mutated Fas ligand (gld) was used to investigate the role of the Fas/FasL system in the regulation of myeloid progenitor cell kinetics.Granulocyte-macrophage colony-forming cells (CFU-GM) were measured by a standard colony assay and the proliferative activity of CFU-GM was measured by replating primary colonies and observing secondary colony formation. Fas expression was restored to lpr mouse bone marrow cells by retrovirus-mediated gene transfer and gld mouse marrow cells were treated with soluble FasL. Wild-type marrow cells were treated with YVAD (a caspase inhibitor) or anti-Fas monoclonal antibodies. There were greater frequencies of myeloid progenitor cells (CFU-GM) in lpr and gld mouse marrow compared to wild-type (WT) marrow (p = 0.0008). The proliferative capacity of CFU-GM was also significantly greater for lpr and gld CFU-GM compared to WT CFU-GM (p = 0.0003 and 0.0001, respectively). Retrovirus-mediated restoration of Fas into lpr marrow, and provision of soluble FasL (sFasL) to gld CFU-GM reduced CFU-GM proliferation to WT levels. Treatment of WT CFU-GM with YVAD or anti-FasL monoclonal antibody increased CFU-GM proliferation to the levels found in lpr and gld CFU-GM. YVAD significantly increased and anti-Fas significantly reduced the proliferative capacity of human CFU-GM (p = 0.015 and 0.04, respectively).Fas, FasL, and caspase activation may play an important role in regulating myeloid progenitor cell kinetics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0301-472X
pubmed:author
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1428-35
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
A role for the Fas/Fas ligand apoptotic pathway in regulating myeloid progenitor cell kinetics.
pubmed:affiliation
LRF Centre For Adult Leukaemia, Department of Haematology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Campus, DuCane Road, London W12 0NN, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't