Document Detail

Downregulation of CXCR4 gene expression in primary human endothelial cells following infection with E1(-)E4(+) adenovirus gene transfer vectors.
MedLine Citation:
PMID:  11020354     Owner:  NLM     Status:  MEDLINE    
Infection of human endothelial cells with first-generation E1(-)E4(+) adenovirus (Ad) vectors leads to prolonged cell survival and changes in the cell phenotype to a more quiescent stage. Based on the concept that the CXCR4, the receptor for the endothelial chemoattractant stromal-derived factor-&alpha (SDF-alpha), is constitutively expressed by quiescent, resting endothelial cells, the present study analyzes the effect of Ad vector infection on CXCR4 expression and SDF-alpha responses of human umbilical vein endothelial cells (HUVEC). CXCR4 transcripts were markedly downregulated in E1(-)E4(+) Ad-infected cells 48 h following infection, but not in uninfected control cells or when the cells were infected with an E1(-)E4(-) Ad vector. Analysis of surface CXCR4 expression by flow cytometry demonstrated marked reduction of the CXCR4 receptor on cells infected with E1(-)E4(+) Ad compared to uninfected control cells or E1(-)E4(-) Ad-infected cells. Infection of other cell types which express CXCR4, such as dendritic cells and myeloma cells, did not exhibit CXCR4 receptor downregulation following infection with E1(-)E4(+) Ad. Consistent with the observed downregulation of CXCR4 mRNA and surface protein, infection of the endothelial cells with an E1(-)E4(+) Ad rendered the cells unresponsive to the chemoattractant SDF-alpha compared to naive or E1(-)E4(-) Ad-infected cells. Together, the data suggest that first-generation Ad vectors, likely the E4 region, modify the ability of endothelial cells to respond to at least one important chemoattractant.
R Ramalingam; S Worgall; S Rafii; R G Crystal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  2     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-11-02     Completed Date:  2000-11-15     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  381-6     Citation Subset:  IM    
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University-New York Presbyterian Hospital, New York, New York 94143, USA.
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MeSH Terms
Adenoviridae / genetics*
Adenovirus E1 Proteins / genetics*
Adenovirus E4 Proteins / genetics*
Blotting, Northern
Cells, Cultured
Endothelium, Vascular / metabolism*
Flow Cytometry
Gene Expression
Gene Therapy
Gene Transfer Techniques
Genetic Vectors
Neovascularization, Pathologic / therapy
RNA, Messenger / metabolism*
Receptors, CXCR4 / genetics*,  metabolism
beta-Galactosidase / metabolism
Grant Support
Reg. No./Substance:
0/Adenovirus E1 Proteins; 0/Adenovirus E4 Proteins; 0/RNA, Messenger; 0/Receptors, CXCR4; EC

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