Inhibition of allergic responsiveness in a murine asthma model via IFN-gamma transgene expression.
OBJECTIVE
To investigate adenoviral vector mediated exogenous gene expression in mouse lungs and the effect of mIFN-gamma transgene expression on allergen-induced pulmonary eosinophil infiltration in a murine asthmatic model.


METHODS
LacZ marker gene was transduced into CD-1 mouse airway epithelial cells by installation of a replication-deficient adenovirus with LacZ gene (AdCMVLacZ) 5 x 10(9) plaque forming unit (pfu) in the intratrachea or nostril. C57 mice were sensitized intraperitoneally and challenged by aerosol with ovalbumin (OVA) to produce an asthmatic model. AdCMVmIFNgamma 5 x 10(9) pfu was administered via nostril in asthmatic mice 48 h before OVA challenge. Sera, bronchial alveolar lavage (BAL) and lungs were recovered 48 h after OVA challenge.


RESULTS
After administration with AdCMVLacZ by intratracheal installation or nose-drop, the lungs revealed a high level of widespread LacZ transduction with X-gal staining, mainly along airways. IFN-gamma via adenoviral vector transduction could be overexpressed both in vitro and in vivo (1624.7 +/- 1321.5 pg/ml in BAL 96 h after AdCMVIFNgamma infection). In AdCMVIFNgamma treated asthmatic models, histological evaluation revealed marked suppression of eosinophil peribronchial and perivascular infiltration; the recoverable percentage of eosinophils in BAL was an average of 9.00% +/- 4.58%, which was a statistically significant decrease versus that of the positive control group (75.13% +/- 6.85%) (P < 0.001). The total cell number in BAL ((145 +/- 55.6) x 10(3) cells/ml) in AdCMVmIFNgamma treated mice also was tremendously reduced compared to the positive control group ((216.6 +/- 71.1) x 10(3) cells/ml).


CONCLUSIONS
Adenoviral vector was able to overexpress exogenous gene in murine lungs. IFN-gamma overexpression via adenoviral vector in pulmonary epithelia in vivo can abrogate allergen-induced eosinophilic infiltration in lungs in an asthmatic model, which may suggest a new preventively therapeutic method for cytokine immunogenetic transfer in allergic asthma.
Gao
Zhancheng
Z
Department of Respiratory Medicine, Peking University People's Hospital, Beijing 100044, China.
Kang
Yu
Y
Xu
Yu
Y
Shang
Ying
Y
Gai
Jun
J
He
Quanying
Q
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001249:Asthma / Q000628:therapy*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000517:prevention & control*; D015316:Genetic Therapy; D007371:Interferon-gamma / Q000235:genetics*; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D019076:Transgenes
D007371:Interferon-gamma; D010047:Ovalbumin