Downregulation of CXCR4 gene expression in primary human endothelial cells following infection with E1-E4+ adenovirus gene transfer vectors

Ramachandran Ramalingam, Stefan Worgall, Shahin Rafii, Ronald Crystal

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Infection of human endothelial cells with first-generation El-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-1α (SDF-1α), is constitutively expressed by quiescent, resting endothelial cells, the present study analyzes the effect of Ad vector infection on CXCR4 expression and SDF-1α 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 un infected 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 un infected 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-1α 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.

Original languageEnglish
Pages (from-to)381-386
Number of pages6
JournalMolecular Therapy
Volume2
Issue number4
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Fingerprint

Adenoviridae
Down-Regulation
Endothelial Cells
Gene Expression
Infection
Genes
CXCR4 Receptors
Chemotactic Factors
Adenoviridae Infections
Human Umbilical Vein Endothelial Cells
Dendritic Cells
Cell Survival
Flow Cytometry
Membrane Proteins
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Downregulation of CXCR4 gene expression in primary human endothelial cells following infection with E1-E4+ adenovirus gene transfer vectors. / Ramalingam, Ramachandran; Worgall, Stefan; Rafii, Shahin; Crystal, Ronald.

In: Molecular Therapy, Vol. 2, No. 4, 01.01.2000, p. 381-386.

Research output: Contribution to journalArticle

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