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
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
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.
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U2 - 10.1016/S0003-4975(97)00367-6
DO - 10.1016/S0003-4975(97)00367-6
M3 - Article
C2 - 9205148
AN - SCOPUS:0030860603
SN - 0003-4975
VL - 63
SP - 1562
EP - 1567
JO - Annals of Thoracic Surgery
JF - Annals of Thoracic Surgery
IS - 6
ER -