Adenovirus-mediated erythropoietin production by airway epithelia is enhanced by apical localization of the coxsackie-adenovirus receptor in vivo

Benjamin Davis; Jenny Nguyen; David Stoltz; Dayna Depping; Katherine J D Excoffon; Joseph Zabner

doi:10.1016/j.ymthe.2004.05.032

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Adenovirus-mediated erythropoietin production by airway epithelia is enhanced by apical localization of the coxsackie-adenovirus receptor in vivo

Journal article

Open access

Peer reviewed

Adenovirus-mediated erythropoietin production by airway epithelia is enhanced by apical localization of the coxsackie-adenovirus receptor in vivo

Benjamin Davis, Jenny Nguyen, David Stoltz, Dayna Depping, Katherine J D Excoffon and Joseph Zabner

Molecular therapy, Vol.10(3), pp.500-506

09/2004

DOI: 10.1016/j.ymthe.2004.05.032

PMID: 15336650

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Abstract

In well-differentiated human airway epithelia, the coxsackie B and adenovirus types 2 and 5 receptor (CAR) resides on the basolateral membrane. Replacing the transmembrane and cytoplasmic tail of CAR with a glycosyl-phosphatidylinositol anchor (GPI-CAR) allows apical localization of GPI-CAR, where it can bind adenovirus and enhance gene transfer in vitro. To test this hypothesis further and to investigate requirements and barriers we developed an in vivo model that quantitatively assesses gene transfer of erythropoietin (EPO) to mouse airway epithelia. Our data suggest that erythropoietin is secreted basolaterally, allowing possible access to the bloodstream. The data also suggest that basolateral adenovirus-mediated airway epithelia EPO secretion persists for long periods and could be used to study persistence in vivo. Additionally, the increase in hematocrit in response to the increased serum EPO could be used for therapeutic purposes. Finally, we tested the ability of apically localized CAR to enhance the infection of AdEPO in mouse airway epithelia in vivo. The data suggest that apical receptors in airway epithelia may be sufficient to improve adenovirus infection of airway epithelia in vivo.

Cell Polarity

Gene Transfer Techniques

Epithelial Cells - metabolism

Receptors, Virus - metabolism

Humans

Mice, Inbred C57BL

Cells, Cultured

Hematocrit

Macaca mulatta

Coxsackie and Adenovirus Receptor-Like Membrane Protein

Erythropoietin - genetics

Animals

Adenoviridae - genetics

Lung - metabolism

Mice

Respiratory Mucosa - metabolism

Erythropoietin - biosynthesis

Genes, Reporter

Details

Title: Subtitle: Adenovirus-mediated erythropoietin production by airway epithelia is enhanced by apical localization of the coxsackie-adenovirus receptor in vivo
Creators: Benjamin Davis - Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, 440 EMRB, Iowa City, IA 52242, USA
Jenny Nguyen
David Stoltz
Dayna Depping
Katherine J D Excoffon
Joseph Zabner
Resource Type: Journal article
Publication Details: Molecular therapy, Vol.10(3), pp.500-506
DOI: 10.1016/j.ymthe.2004.05.032
PMID: 15336650
NLM abbreviation: Mol Ther
ISSN: 1525-0016
eISSN: 1525-0024
Publisher: United States
Grant note: HL51670-10 / NHLBI NIH HHS DK54759 / NIDDK NIH HHS
Language: English
Date published: 09/2004
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Immunology; Internal Medicine
Record Identifier: 9984025315602771

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