Linked Life Data

9376117

Source:http://linkedlifedata.com/resource/pubmed/id/9376117

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-11-12
pubmed:abstractText
Recombinant adenoviruses are currently being evaluated as gene transfer vectors for the treatment of airway diseases. Recent evidence indicates that gene transfer to differentiated airway epithelial cells is inefficient. We hypothesized that apical membrane glycoconjugates, such as the transmembrane mucin MUC1, reduce the efficiency of adenovirus-mediated gene transfer. To address this, studies were performed in primary bronchial epithelial and Madin Darby canine kidney (MDCK) cells transduced to express human MUC1. Colocalization of MUC1 and an adenoviral lacZ transgene in the bronchial epithelial cells revealed that at several multiplicities of infection, the percentage of cells expressing lacZ was five-fold less in MUC1-expressing cells. Moreover, lacZ expression was three- to eight-fold lower in MUC1-expressing than in control MDCK cells, demonstrating that MUC1 interferes with gene transfer and is not merely a phenotypic marker of a cell that is refractory to adenovirus infection. Neuraminidase pretreatment of cells to remove sialic acid residues prior to viral adsorption increased the efficiency of gene transfer two- to five-fold in human airway and MDCK cells, and in a xenograft model of human airway. This effect was also observed in cultured cells that do not express MUC1, suggesting that other sialylated glycoconjugates impact on the efficiency of gene transfer. An inhibitory effect of negatively charged glycoconjugates on adenovirus binding was further supported by the finding that adsorption of adenovirus with a polycation significantly increased gene transfer efficiency. These data demonstrate for the first time that sialoglycoconjugates on epithelial cells reduce the efficiency of adenovirus-mediated gene transfer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
422-35
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
MUC1 and other sialoglycoconjugates inhibit adenovirus-mediated gene transfer to epithelial cells.
pubmed:affiliation
Department of Medicine, University of Pittsburgh, Pennsylvania, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't