In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery

P. Lemarchand, M. Jones, C. Danel, I. Yamada, A. Mastrangeli, Ronald Crystal

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 languageEnglish
Pages (from-to)2840-2845
Number of pages6
JournalJournal of Applied Physiology
Volume76
Issue number6
Publication statusPublished - 21 Jun 1994
Externally publishedYes

Fingerprint

Pulmonary Circulation
Adenoviridae
Pulmonary Artery
Lung
Genes
Epithelium
Endothelium
Sheep
Galactosidases
Bronchioles
Gene Expression
Lac Operon
Pulmonary Veins
Bronchi
Reporter Genes
Endothelial Cells
Epithelial Cells
Escherichia coli

Keywords

  • cystic fibrosis
  • endothelium
  • epithelium
  • pulmonary circulation

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Lemarchand, P., Jones, M., Danel, C., Yamada, I., Mastrangeli, A., & Crystal, R. (1994). In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery. Journal of Applied Physiology, 76(6), 2840-2845.

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 journalArticle

Lemarchand, P, Jones, M, Danel, C, Yamada, I, Mastrangeli, A & Crystal, R 1994, 'In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery', Journal of Applied Physiology, vol. 76, no. 6, pp. 2840-2845.
Lemarchand P, Jones M, Danel C, Yamada I, Mastrangeli A, Crystal R. In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery. Journal of Applied Physiology. 1994 Jun 21;76(6):2840-2845.
Lemarchand, P. ; Jones, M. ; Danel, C. ; Yamada, I. ; Mastrangeli, A. ; Crystal, Ronald. / In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery. In: Journal of Applied Physiology. 1994 ; Vol. 76, No. 6. pp. 2840-2845.
@article{2d7f9c8b8cdd4a72acebea8987becdcf,
title = "In vivo adenovirus-mediated gene transfer to lungs via pulmonary artery",
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.",
keywords = "cystic fibrosis, endothelium, epithelium, pulmonary circulation",
author = "P. Lemarchand and M. Jones and C. Danel and I. Yamada and A. Mastrangeli and Ronald Crystal",
year = "1994",
month = "6",
day = "21",
language = "English",
volume = "76",
pages = "2840--2845",
journal = "Journal of Applied Physiology",
issn = "8750-7587",
publisher = "American Physiological Society",
number = "6",

}

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 -