Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome- mediated endothelin-1 gene transfer

Shin Ichi Takeda, Yoshiki Sawa, Masato Minami, Yasufumi Kaneda, Yoshitaka Fujii, Ryota Shirakura, Masashi Yanagisawa, Hikaru Matsuda

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background. Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 lET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. Methods. We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)- liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with β-galactosidase gene was introduced. The expression of ET-1 and β- galactosidase was assessed by immunohistochemistry. Results. Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of β-galactosidase gene, indicating β-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. Conclusions. These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.

Original languageEnglish (US)
Pages (from-to)1562-1567
Number of pages6
JournalAnnals of Thoracic Surgery
Volume63
Issue number6
DOIs
StatePublished - Jun 1997

Fingerprint

Bronchiolitis Obliterans
Sendai virus
Endothelin-1
Liposomes
Galactosidases
Alveolar Epithelial Cells
Genes
Transfection
Epithelial Cells
High Mobility Group Proteins
Heart-Lung Transplantation
Connective Tissue Cells
Membrane Fusion
Granulation Tissue
Lung Transplantation
Endothelins
Alveolar Macrophages
Connective Tissue
Blood Vessels
Disease Progression

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Takeda, S. I., Sawa, Y., Minami, M., Kaneda, Y., Fujii, Y., Shirakura, R., ... Matsuda, H. (1997). Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome- mediated endothelin-1 gene transfer. Annals of Thoracic Surgery, 63(6), 1562-1567. https://doi.org/10.1016/S0003-4975(97)00367-6

Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome- mediated endothelin-1 gene transfer. / Takeda, Shin Ichi; Sawa, Yoshiki; Minami, Masato; Kaneda, Yasufumi; Fujii, Yoshitaka; Shirakura, Ryota; Yanagisawa, Masashi; Matsuda, Hikaru.

In: Annals of Thoracic Surgery, Vol. 63, No. 6, 06.1997, p. 1562-1567.

Research output: Contribution to journalArticle

Takeda, Shin Ichi ; Sawa, Yoshiki ; Minami, Masato ; Kaneda, Yasufumi ; Fujii, Yoshitaka ; Shirakura, Ryota ; Yanagisawa, Masashi ; Matsuda, Hikaru. / Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome- mediated endothelin-1 gene transfer. In: Annals of Thoracic Surgery. 1997 ; Vol. 63, No. 6. pp. 1562-1567.
@article{8efa6fe98c194f90838e66dd120687b2,
title = "Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome- mediated endothelin-1 gene transfer",
abstract = "Background. Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 lET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. Methods. We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)- liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with β-galactosidase gene was introduced. The expression of ET-1 and β- galactosidase was assessed by immunohistochemistry. Results. Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of β-galactosidase gene, indicating β-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. Conclusions. These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.",
author = "Takeda, {Shin Ichi} and Yoshiki Sawa and Masato Minami and Yasufumi Kaneda and Yoshitaka Fujii and Ryota Shirakura and Masashi Yanagisawa and Hikaru Matsuda",
year = "1997",
month = "6",
doi = "10.1016/S0003-4975(97)00367-6",
language = "English (US)",
volume = "63",
pages = "1562--1567",
journal = "Annals of Thoracic Surgery",
issn = "0003-4975",
publisher = "Elsevier USA",
number = "6",

}

TY - JOUR

T1 - Experimental bronchiolitis obliterans induced by in vivo HVJ-liposome- mediated endothelin-1 gene transfer

AU - Takeda, Shin Ichi

AU - Sawa, Yoshiki

AU - Minami, Masato

AU - Kaneda, Yasufumi

AU - Fujii, Yoshitaka

AU - Shirakura, Ryota

AU - Yanagisawa, Masashi

AU - Matsuda, Hikaru

PY - 1997/6

Y1 - 1997/6

N2 - Background. Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 lET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. Methods. We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)- liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with β-galactosidase gene was introduced. The expression of ET-1 and β- galactosidase was assessed by immunohistochemistry. Results. Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of β-galactosidase gene, indicating β-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. Conclusions. These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.

AB - Background. Bronchiolitis obliterans (OB) is a lesion that results when injury to small conducting airways is repaired by a proliferation of fibrous granulation tissue. Bronchiolitis obliterans has emerged as a main cause of morbidity and mortality in the setting of lung and heart-lung transplantation. Endothelin-1 lET-1), initially discovered as a vasoconstrictive peptide, has a mitogenic activity on vascular smooth cells and airway epithelial cells. Overproduction of endothelin has been reported in patients with OB or chronic rejection after lung transplantation. It is still undetermined whether locally overexpressed ET-1 has a potential impact in the pathogenesis of OB. Methods. We locally overexpressed ET-1 using ultraviolet irradiation-inactivated hemagglutinating virus of Japan (HVJ)- liposome-mediated in vivo gene transfer. Plasmid DNA of prepro-ET-1 and high mobility group 1 protein were coencapsulated in liposomes, and were introduced into airway epithelial cells by HVJ-mediated membrane fusion. Control animals received instillation of HVJ-liposome with an empty expression cassette. To confirm the efficiency of transfection, HVJ liposome with β-galactosidase gene was introduced. The expression of ET-1 and β- galactosidase was assessed by immunohistochemistry. Results. Bronchial epithelium alveolar cells and alveolar macrophage were stained blue (X-Gal) 1 week after in vivo gene transfer of β-galactosidase gene, indicating β-gal activity. In animals 1 to 2 weeks after in vivo transfection of prepro-ET-1 gene, hyperplastic connective tissue plaque was seen in the alveolar duct and small conducting airway, indicating histologically distinctive bronchiolitis obliterans. Strong ET-1-like immunoactivities were seen in the airway epithelial, hyperplastic connective tissue, and alveolar cells. No histopathologic changes were seen in the control animals. Conclusions. These results suggested that ET-1 may play an important role in the pathogenesis of OB. The effective pharmacologic antagonist or inhibitor may possibly control the progression of disease in patients of OB.

UR - http://www.scopus.com/inward/record.url?scp=0030860603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030860603&partnerID=8YFLogxK

U2 - 10.1016/S0003-4975(97)00367-6

DO - 10.1016/S0003-4975(97)00367-6

M3 - Article

C2 - 9205148

AN - SCOPUS:0030860603

VL - 63

SP - 1562

EP - 1567

JO - Annals of Thoracic Surgery

JF - Annals of Thoracic Surgery

SN - 0003-4975

IS - 6

ER -