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Inhibition of epithelial sodium channels by respiratory syncytial virus in vitro and in vivo
Author(s) -
Song Weifeng,
Wei Shipeng,
Matalon Sadis
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05560.x
Subject(s) - epithelial sodium channel , respiratory system , nasal administration , respiratory tract , in vivo , virus , lung , receptor , chemistry , pharmacology , immunology , sodium , biology , medicine , biochemistry , microbiology and biotechnology , organic chemistry
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection in infants and children worldwide. Infection of mice with RSV decreased sodium (Na + ) dependent alveolar fluid clearance (AFC), resulting in increased lung water content and hypoxemia. RSV infection resulted in higher levels of pyrimidines and purines in the alveolar space. Intratracheal administration of UTP or UDP also decreased AFC. The effects of RSV on AFC and oxygen saturation of Balb/c mice were reversed by intraalveolar administration of antagonists of P2Y nucleotide receptors, enzymes that enhance the breakdown of pyrimidines and systemic or intranasal administration of inhibitors of the de novo pathway of pyrimidine synthesis. RSV infection of H441 or mouse tracheal epithelial cells decreased the amiloride‐sensitive Na + currents and pretreatment of H441 cells with A77 prevented this effect. These findings indicate that the harmful effects of RSV on lung epithelia are mediated at least in part via the production of UTP and its paracrine action on ENaC.