Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-12-16
pubmed:abstractText
Neutrophils are a critical component of the innate immune response to invading microbial pathogens. However, an excessive and/or prolonged neutrophil response can result in tissue injury that is thought to underlie the pathogenesis of various inflammatory diseases. The development of novel therapeutic strategies for inflammatory diseases depends on an improved understanding of regulation of neutrophil function. However, investigations into neutrophil function have been constrained in part by the difficulty of genetically modifying neutrophils using current techniques. To overcome this, we have developed a novel method for the genetic modification of murine bone marrow derived progenitor cells using retroviral transduction followed by long term bone marrow culture to generate mature neutrophils. These neutrophils are functionally mature as determined by morphology, surface marker (Gr1, CD11b, CD62L and CXCR2) expression, and functional attributes including the ability to generate superoxide, exocytose granule contents, chemotax, and phagocytose and kill bacteria. Further, the in vitro matured neutrophils are capable of migrating to an inflammatory site in vivo. We utilized this system to express the Bcl-2 transgene in mature neutrophils using the retroviral vectors pMIG and pMIT. Bcl-2 overexpression conferred a substantial delay in spontaneous apoptosis of neutrophils as assessed by annexin V and 7-amino-actinomycin D (7AAD) staining. Moreover, Bcl-2 overexpression did not alter granulopoiesis, as assessed by morphology and surface marker expression. This system enables the genetic manipulation of progenitor cells that can be differentiated in vitro to mature neutrophils that are functional in vitro and in vivo.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-10088605, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-10611317, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-10657669, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-10793167, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-11163351, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-11323692, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-12370261, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-12391245, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-12433687, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-12483108, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-12763940, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-14694182, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-14699155, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-15061567, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-15240889, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-1536952, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-16200064, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-17018860, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-17062731, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-17082641, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-17634277, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-17785775, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-18039095, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-18252915, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-18578569, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-1871110, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-301143, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-3814822, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-476301, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-6096475, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-6669951, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-8025271, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-8113673, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-8394011, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-9003774, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-90108, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-9028316, http://linkedlifedata.com/resource/pubmed/commentcorrection/19010330-9923446
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1759
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
340
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
102-15
pubmed:dateRevised
2011-5-2
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
A novel method for long term bone marrow culture and genetic modification of murine neutrophils via retroviral transduction.
pubmed:affiliation
Department of Medicine, National Jewish Health, Denver, CO, United States.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural