Linked Life Data

14625570

Source:http://linkedlifedata.com/resource/pubmed/id/14625570

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2003-11-19
pubmed:abstractText
Inadequate antiprotease activity in the lungs due to alpha-1-antitrypsin (A1AT) deficiency is a factor of early-onset emphysema. We propose a new approach to gene therapy that involves the intratracheal delivery of macrophages expressing human A1AT (hA1AT). Recombinant adeno-associated virus (rAAV) plasmids encoding the hA1AT gene were packaged into virions using 293 cells, and transgenic progeny virus was purified from the cells. The murine macrophage cell line J774A.1 was infected in vitro with the recombinant hA1AT rAAV virus. The hA1AT-producing macrophages were delivered intratracheally into mechanically ventilated C57BL/6J mice, a strain with low endogenous levels of A1AT. Transcription of hA1AT mRNA was detected in the transfected cells by RT-PCR, and protein expression was verified by immunohistochemistry. Levels of hA1AT in the cell culture medium and in the bronchoalveolar lavage (BAL) were assayed by ELISA. The concentration of hA1AT in J774A.1 cell-conditioned medium increased from undetectable levels prior to transfection, to 60 mg/l at 24 h post-transfection. At 1, 3 and 7 days after intratracheal delivery of transfected macrophages, hA1AT protein in BAL from C57BL/6J mice increased from undetectable levels to 2.5+/-0.9, 2.6+/-1.1 and 2.2+/-0.8 mg/l, respectively. These results suggest that airway delivery of macrophages overexpressing hA1AT may be an effective approach to enhance alveolar protection in A1AT deficiency.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2148-52
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Alpha-1-antitrypsin expression in the lung is increased by airway delivery of gene-transfected macrophages.
pubmed:affiliation
College of Medicine, University of Cincinnati, Cincinnati, OH 45267, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.