Abstract
On the basis of the knowledge that the pulmonary and bronchial circulations have extensive anastomoses, we hypothesized that gene transfer to the endothelium of both pulmonary and bronchial circulations might be achieved with replication-deficient recombinant adenovirus (Ad) vectors administered to the pulmonary circulation. To evaluate this concept, the right upper lobe branches of the sheep pulmonary artery and vein were temporarily occluded and a replication-deficient recombinant Ad vector containing the Escherichia coli lacZ reporter gene coding for β- galactosidase (β-Gal) was infused into the lumen of the occluded pulmonary artery. After 15 min, the pulmonary circulation was restored, and 1 or 4 days later the lungs were evaluated by histochemical analysis for β-Gal activity. Gene transfer and expression were positive in 13 of 17 evaluated sheep. No β-Gal activity was detected in any category of cells of uninfected lobes. As hypothesized, β-Gal activity was detected in endothelial cells of the right upper lobe pulmonary and bronchial circulations. Unexpectedly, gene transfer was also observed in epithelial cells of the alveoli and the airways (bronchi and bronchioles) as well as in the epithelium of submucosal glands. These studies demonstrate that it is possible to use Ad vectors for transfer and expression of genes to lung parenchymal cells served by both the pulmonary and bronchial circulations. Furthermore, whereas administration of such vectors via the airways results in gene transfer only to the epithelium, pulmonary artery administration permits gene transfer to both endothelium and epithelium, thus expanding the target range of Ad gene transfer to the lungs.
| Original language | English |
|---|---|
| Pages (from-to) | 2840-2845 |
| Number of pages | 6 |
| Journal | Journal of Applied Physiology |
| Volume | 76 |
| Issue number | 6 |
| Publication status | Published - 21 Jun 1994 |
| Externally published | Yes |
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Keywords
- cystic fibrosis
- endothelium
- epithelium
- pulmonary circulation
ASJC Scopus subject areas
- Physiology
- Physiology (medical)
Cite this
In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery. / Lemarchand, P.; Jones, M.; Danel, C.; Yamada, I.; Mastrangeli, A.; Crystal, Ronald.
In: Journal of Applied Physiology, Vol. 76, No. 6, 21.06.1994, p. 2840-2845.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery
AU - Lemarchand, P.
AU - Jones, M.
AU - Danel, C.
AU - Yamada, I.
AU - Mastrangeli, A.
AU - Crystal, Ronald
PY - 1994/6/21
Y1 - 1994/6/21
N2 - On the basis of the knowledge that the pulmonary and bronchial circulations have extensive anastomoses, we hypothesized that gene transfer to the endothelium of both pulmonary and bronchial circulations might be achieved with replication-deficient recombinant adenovirus (Ad) vectors administered to the pulmonary circulation. To evaluate this concept, the right upper lobe branches of the sheep pulmonary artery and vein were temporarily occluded and a replication-deficient recombinant Ad vector containing the Escherichia coli lacZ reporter gene coding for β- galactosidase (β-Gal) was infused into the lumen of the occluded pulmonary artery. After 15 min, the pulmonary circulation was restored, and 1 or 4 days later the lungs were evaluated by histochemical analysis for β-Gal activity. Gene transfer and expression were positive in 13 of 17 evaluated sheep. No β-Gal activity was detected in any category of cells of uninfected lobes. As hypothesized, β-Gal activity was detected in endothelial cells of the right upper lobe pulmonary and bronchial circulations. Unexpectedly, gene transfer was also observed in epithelial cells of the alveoli and the airways (bronchi and bronchioles) as well as in the epithelium of submucosal glands. These studies demonstrate that it is possible to use Ad vectors for transfer and expression of genes to lung parenchymal cells served by both the pulmonary and bronchial circulations. Furthermore, whereas administration of such vectors via the airways results in gene transfer only to the epithelium, pulmonary artery administration permits gene transfer to both endothelium and epithelium, thus expanding the target range of Ad gene transfer to the lungs.
AB - On the basis of the knowledge that the pulmonary and bronchial circulations have extensive anastomoses, we hypothesized that gene transfer to the endothelium of both pulmonary and bronchial circulations might be achieved with replication-deficient recombinant adenovirus (Ad) vectors administered to the pulmonary circulation. To evaluate this concept, the right upper lobe branches of the sheep pulmonary artery and vein were temporarily occluded and a replication-deficient recombinant Ad vector containing the Escherichia coli lacZ reporter gene coding for β- galactosidase (β-Gal) was infused into the lumen of the occluded pulmonary artery. After 15 min, the pulmonary circulation was restored, and 1 or 4 days later the lungs were evaluated by histochemical analysis for β-Gal activity. Gene transfer and expression were positive in 13 of 17 evaluated sheep. No β-Gal activity was detected in any category of cells of uninfected lobes. As hypothesized, β-Gal activity was detected in endothelial cells of the right upper lobe pulmonary and bronchial circulations. Unexpectedly, gene transfer was also observed in epithelial cells of the alveoli and the airways (bronchi and bronchioles) as well as in the epithelium of submucosal glands. These studies demonstrate that it is possible to use Ad vectors for transfer and expression of genes to lung parenchymal cells served by both the pulmonary and bronchial circulations. Furthermore, whereas administration of such vectors via the airways results in gene transfer only to the epithelium, pulmonary artery administration permits gene transfer to both endothelium and epithelium, thus expanding the target range of Ad gene transfer to the lungs.
KW - cystic fibrosis
KW - endothelium
KW - epithelium
KW - pulmonary circulation
UR - http://www.scopus.com/inward/record.url?scp=0028286047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028286047&partnerID=8YFLogxK
M3 - Article
C2 - 7928919
AN - SCOPUS:0028286047
VL - 76
SP - 2840
EP - 2845
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
SN - 8750-7587
IS - 6
ER -