| 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 |
Abstract/OtherAbstract:
|
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. |
| | |
Authors:
|
R Ramalingam; S Worgall; S Rafii; R G Crystal |
Related Documents
:
|
23297114 - Hydrogen sulfide reduces cell adhesion and relevant inflammatory triggering by preventi... 23676504 - Integrins-fak-rho gtpases pathway in endothelial cells sense and response to surface we... 19700624 - Nitrite enhances rbc hypoxic atp synthesis and the release of atp into the vasculature:... 17094094 - Adherent leukocytes capture sickle erythrocytes in an in vitro flow model of vaso-occlu... 1371684 - Nitric oxide but not prostacyclin is an autocrine endothelial mediator. 8948574 - Ooplasmic redistribution in tubifex eggs with selectively impaired cortical actin cytos... |
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 |
Affiliation:
|
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University-New York Presbyterian Hospital, New York, New York 94143, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Adenoviridae
/
genetics* Adenovirus E1 Proteins / genetics* Adenovirus E4 Proteins / genetics* Blotting, Northern Cells, Cultured Down-Regulation Endothelium, Vascular / metabolism* Flow Cytometry Gene Expression Gene Therapy Gene Transfer Techniques Genetic Vectors Humans Neovascularization, Pathologic / therapy RNA, Messenger / metabolism* Receptors, CXCR4 / genetics*, metabolism Transfection beta-Galactosidase / metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
R01 HL 57318/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Adenovirus E1 Proteins; 0/Adenovirus E4 Proteins; 0/RNA, Messenger; 0/Receptors, CXCR4; EC 3.2.1.23/beta-Galactosidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reexpression following readministration of an adenoviral vector in adult mice after initial in utero...
Next Document: Effect of preexisting anti-herpes immunity on the efficacy of herpes simplex viral therapy in a muri...